chr16-30700951-G-T

Variant names:

• chr16-30700951-G-T
• rs73536498
• NM_006662.3:c.54+73G>T

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_006662.3(SRCAP):​c.54+73G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00568 in 1,513,484 control chromosomes in the GnomAD database, including 389 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.029 (188 hom., cov: 32)
  • Exomes 𝑓: 0.0031 (201 hom.)
• Consequence: SRCAP NM_006662.3 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.748
• Publications: 0 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

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BP6: Variant 16-30700951-G-T is Benign according to our data. Variant chr16-30700951-G-T is described in ClinVar as Benign. ClinVar VariationId is 1304879.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.101 is higher than 0.05.

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.54+73G>T		intron	N/A	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.54+73G>T		intron	N/A	ENSP00000262518.4	Q6ZRS2-1
	SRCAP	ENST00000411466.7	TSL:3	c.54+73G>T		intron	N/A	ENSP00000405186.3	C9J4U4
	SRCAP	ENST00000706321.1		c.54+73G>T		intron	N/A	ENSP00000516346.1	Q6ZRS2-1

Frequencies

GnomAD3 genomes AF: 0.0290 AC: 4409 AN: 152178 Hom.: 182 Cov.: 32

Gnomad AFR AF: 0.103

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00550

Gnomad ASJ AF: 0.00115

Gnomad EAS AF: 0.000385

Gnomad SAS AF: 0.000414

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000220

Gnomad OTH AF: 0.0182

GnomAD4 exome AF: 0.00306 AC: 4165 AN: 1361188 Hom.: 201 AF XY: 0.00255 AC XY: 1739 AN XY: 681642

African (AFR) AF: 0.110 AC: 3440 AN: 31376

American (AMR) AF: 0.00460 AC: 202 AN: 43898

Ashkenazi Jewish (ASJ) AF: 0.00147 AC: 37 AN: 25246

East Asian (EAS) AF: 0.00118 AC: 46 AN: 39000

South Asian (SAS) AF: 0.000228 AC: 19 AN: 83516

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52914

Middle Eastern (MID) AF: 0.00144 AC: 8 AN: 5558

European-Non Finnish (NFE) AF: 0.0000909 AC: 93 AN: 1022650

Other (OTH) AF: 0.00561 AC: 320 AN: 57030

GnomAD4 genome AF: 0.0291 AC: 4439 AN: 152296 Hom.: 188 Cov.: 32 AF XY: 0.0282 AC XY: 2102 AN XY: 74466

African (AFR) AF: 0.103 AC: 4297 AN: 41542

American (AMR) AF: 0.00543 AC: 83 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.00115 AC: 4 AN: 3470

East Asian (EAS) AF: 0.000386 AC: 2 AN: 5186

South Asian (SAS) AF: 0.00 AC: 0 AN: 4828

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10622

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.000220 AC: 15 AN: 68036

Other (OTH) AF: 0.0180 AC: 38 AN: 2112

Alfa AF: 0.0104 Hom.: 5

Bravo AF: 0.0330

Asia WGS AF: 0.00953 AC: 34 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.19
DANN	Benign	0.68
PhyloP100		-0.75
Mutation Taster		=100/0	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		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: rs73536498; hg19: chr16-30712272;