rs117804715

Variant names:

• chr16-30724027-C-G
• rs117804715
• NM_006662.3:c.4603C>G

Your query was ambiguous. Multiple possible variants found:

• chr16-30724027-C-G
• chr16-30724027-C-T
• chr16-30724027-C-A

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BS1 BS2

The NM_006662.3(SRCAP):​c.4603C>G​(p.Pro1535Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00759 in 1,613,988 control chromosomes in the GnomAD database, including 65 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. P1535S) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.0066 (3 hom., cov: 32)
  • Exomes 𝑓: 0.0077 (62 hom.)
• Consequence: SRCAP NM_006662.3 missense
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:9
• Conservation: PhyloP100: 0.783
• Publications: 11 publications found

Genes affected

SRCAP (HGNC:16974): (Snf2 related CREBBP activator protein) This gene encodes the core catalytic component of the multiprotein chromatin-remodeling SRCAP complex. The encoded protein is an ATPase that is necessary for the incorporation of the histone variant H2A.Z into nucleosomes. It can function as a transcriptional activator in Notch-mediated, CREB-mediated and steroid receptor-mediated transcription. Mutations in this gene cause Floating-Harbor syndrome, a rare disorder characterized by short stature, language deficits and dysmorphic facial features. [provided by RefSeq, Feb 2012]

SRCAP Gene-Disease associations (from GenCC):

• developmental delay, hypotonia, musculoskeletal defects, and behavioral abnormalities

  Inheritance: AD Classification: DEFINITIVE, STRONG Submitted by: Ambry Genetics, G2P, Labcorp Genetics (formerly Invitae), PanelApp Australia
• Floating-Harbor syndrome

  Inheritance: AD Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: G2P, Ambry Genetics, PanelApp Australia, ClinGen, Labcorp Genetics (formerly Invitae), Orphanet

ENSG00000282034 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.003346175).
• BP6: Variant 16-30724027-C-G is Benign according to our data. Variant chr16-30724027-C-G is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 160035.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS1: Variant frequency is greater than expected in population amr. GnomAd4 allele frequency = 0.00661 (1007/152268) while in subpopulation AMR AF = 0.0113 (173/15292). AF 95% confidence interval is 0.00994. There are 3 homozygotes in GnomAd4. There are 454 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.
• BS2: High AC in GnomAd4 at 1007 AD gene.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_006662.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SRCAP	NM_006662.3	MANE Select	c.4603C>G	p.Pro1535Ala	missense	Exon 25 of 34	NP_006653.2	Q6ZRS2-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SRCAP	ENST00000262518.9	TSL:2 MANE Select	c.4603C>G	p.Pro1535Ala	missense	Exon 25 of 34	ENSP00000262518.4	Q6ZRS2-1
	ENSG00000282034	ENST00000380361.7	TSL:2	n.4072C>G		non_coding_transcript_exon	Exon 20 of 31	ENSP00000369719.3	A0A0C4DFX4
	SRCAP	ENST00000411466.7	TSL:3	c.4603C>G	p.Pro1535Ala	missense	Exon 25 of 34	ENSP00000405186.3	C9J4U4

Frequencies

GnomAD3 genomes AF: 0.00661 AC: 1005 AN: 152148 Hom.: 3 Cov.: 32

Gnomad AFR AF: 0.00133

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0113

Gnomad ASJ AF: 0.0242

Gnomad EAS AF: 0.000576

Gnomad SAS AF: 0.00352

Gnomad FIN AF: 0.000660

Gnomad MID AF: 0.0223

Gnomad NFE AF: 0.00932

Gnomad OTH AF: 0.0120

GnomAD2 exomes AF: 0.00723 AC: 1814 AN: 251008 AF XY: 0.00757

Gnomad AFR exome AF: 0.00117

Gnomad AMR exome AF: 0.00720

Gnomad ASJ exome AF: 0.0234

Gnomad EAS exome AF: 0.0000544

Gnomad FIN exome AF: 0.00121

Gnomad NFE exome AF: 0.00931

Gnomad OTH exome AF: 0.00946

GnomAD4 exome AF: 0.00769 AC: 11240 AN: 1461720 Hom.: 62 Cov.: 34 AF XY: 0.00770 AC XY: 5601 AN XY: 727178

African (AFR) AF: 0.00194 AC: 65 AN: 33478

American (AMR) AF: 0.00794 AC: 355 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.0228 AC: 597 AN: 26136

East Asian (EAS) AF: 0.0000252 AC: 1 AN: 39700

South Asian (SAS) AF: 0.00573 AC: 494 AN: 86258

European-Finnish (FIN) AF: 0.00135 AC: 72 AN: 53260

Middle Eastern (MID) AF: 0.0262 AC: 151 AN: 5768

European-Non Finnish (NFE) AF: 0.00805 AC: 8948 AN: 1112002

Other (OTH) AF: 0.00922 AC: 557 AN: 60394

GnomAD4 genome AF: 0.00661 AC: 1007 AN: 152268 Hom.: 3 Cov.: 32 AF XY: 0.00610 AC XY: 454 AN XY: 74452

African (AFR) AF: 0.00137 AC: 57 AN: 41556

American (AMR) AF: 0.0113 AC: 173 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.0242 AC: 84 AN: 3470

East Asian (EAS) AF: 0.000578 AC: 3 AN: 5192

South Asian (SAS) AF: 0.00353 AC: 17 AN: 4822

European-Finnish (FIN) AF: 0.000660 AC: 7 AN: 10612

Middle Eastern (MID) AF: 0.0204 AC: 6 AN: 294

European-Non Finnish (NFE) AF: 0.00934 AC: 635 AN: 68008

Other (OTH) AF: 0.0118 AC: 25 AN: 2112

Alfa AF: 0.00846 Hom.: 9

Bravo AF: 0.00697

TwinsUK AF: 0.00782 AC: 29

ALSPAC AF: 0.00623 AC: 24

ESP6500AA AF: 0.00182 AC: 8

ESP6500EA AF: 0.00860 AC: 74

ExAC AF: 0.00689 AC: 836

Asia WGS AF: 0.00289 AC: 10 AN: 3478

EpiCase AF: 0.0116

EpiControl AF: 0.0109

ClinVar

ClinVar submissions

Significance: Benign/Likely benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	5	not provided (5)
-	-	4	not specified (4)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.076
BayesDel_addAF	Benign	-0.40	T
BayesDel_noAF	Benign	-0.34
CADD	Benign	20
DANN	Uncertain	0.98
DEOGEN2	Benign	0.047	T
Eigen	Benign	-0.50
Eigen_PC	Benign	-0.36
FATHMM_MKL	Benign	0.52	D
LIST_S2	Benign	0.84	T
MetaRNN	Benign	0.0033	T
MetaSVM	Benign	-0.53	T
MutationAssessor	Benign	0.81	L
PhyloP100		0.78
PrimateAI	Benign	0.43	T
PROVEAN	Benign	-1.9	N
REVEL	Benign	0.17
Sift	Uncertain	0.0040	D
Sift4G	Uncertain	0.019	D
Polyphen		0.045	B
Vest4		0.12
MVP		0.17
MPC		0.41
ClinPred		0.011	T
GERP RS		2.5
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.057
gMVP		0.14
Mutation Taster		=97/3	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.040		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs117804715; hg19: chr16-30735348; COSMIC: COSV107284415;