15-66489772-A-G

Variant names:

• chr15-66489772-A-G
• rs368800650
• NM_002755.4:c.1068+9A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BP6_Very_Strong

The NM_006049.4(SNAPC5):​c.*967T>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000226 in 1,601,320 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★★).

• Frequency:
  • Genomes: 𝑓 0.00024 (0 hom., cov: 32)
  • Exomes 𝑓: 0.00022 (1 hom.)
• Consequence: SNAPC5 NM_006049.4 3_prime_UTR
• Clinical Significance: Likely benign reviewed by expert panel B:5
• Conservation: PhyloP100: -0.321
• Publications: 0 publications found

Genes affected

MAP2K1 (HGNC:6840): (mitogen-activated protein kinase kinase 1) The protein encoded by this gene is a member of the dual specificity protein kinase family, which acts as a mitogen-activated protein (MAP) kinase kinase. MAP kinases, also known as extracellular signal-regulated kinases (ERKs), act as an integration point for multiple biochemical signals. This protein kinase lies upstream of MAP kinases and stimulates the enzymatic activity of MAP kinases upon wide variety of extra- and intracellular signals. As an essential component of MAP kinase signal transduction pathway, this kinase is involved in many cellular processes such as proliferation, differentiation, transcription regulation and development. [provided by RefSeq, Jul 2008]

ENSG00000261351 (HGNC:):

SNAPC5 (HGNC:15484): (small nuclear RNA activating complex polypeptide 5) This gene encodes a subunit of the small nuclear RNA (snRNA)-activating protein complex that plays a role in the transcription of snRNA genes. This complex binds to the promoters of snRNA genes transcribed by either RNA polymerase II or III and recruits other regulatory factors to activate snRNA gene transcription. The encoded protein may play a role in stabilizing this complex. A pseudogene of this gene has been identified on chromosome 6. [provided by RefSeq, Jul 2016]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BP6: Variant 15-66489772-A-G is Benign according to our data. Variant chr15-66489772-A-G is described in ClinVar as Likely_benign. ClinVar VariationId is 180895.Status of the report is reviewed_by_expert_panel, 3 stars.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_006049.4. 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
	MAP2K1	NM_002755.4	MANE Select	c.1068+9A>G		intron	N/A	NP_002746.1	Q02750-1
	SNAPC5	NM_006049.4		c.*967T>C		3_prime_UTR	Exon 4 of 4	NP_006040.1	O75971-1
	MAP2K1	NM_001411065.1		c.924+9A>G		intron	N/A	NP_001397994.1	A0A8I5KYS7

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MAP2K1	ENST00000307102.10	TSL:1 MANE Select	c.1068+9A>G		intron	N/A	ENSP00000302486.5	Q02750-1
	ENSG00000261351	ENST00000565387.2	TSL:1	n.1054T>C		non_coding_transcript_exon	Exon 2 of 2
	MAP2K1	ENST00000685172.1		c.1022+496A>G		intron	N/A	ENSP00000509604.1	A0A8I5KYB4

Frequencies

GnomAD3 genomes AF: 0.000231 AC: 35 AN: 151504 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.000169

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000329

Gnomad ASJ AF: 0.00379

Gnomad EAS AF: 0.000192

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000133

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.000310 AC: 78 AN: 251454 AF XY: 0.000228

Gnomad AFR exome AF: 0.000123

Gnomad AMR exome AF: 0.000202

Gnomad ASJ exome AF: 0.00446

Gnomad EAS exome AF: 0.0000544

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000185

Gnomad OTH exome AF: 0.000326

GnomAD4 exome AF: 0.000225 AC: 326 AN: 1449698 Hom.: 1 Cov.: 29 AF XY: 0.000231 AC XY: 167 AN XY: 721540

African (AFR) AF: 0.0000898 AC: 3 AN: 33394

American (AMR) AF: 0.000247 AC: 11 AN: 44530

Ashkenazi Jewish (ASJ) AF: 0.00465 AC: 120 AN: 25780

East Asian (EAS) AF: 0.0000252 AC: 1 AN: 39690

South Asian (SAS) AF: 0.0000232 AC: 2 AN: 86204

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53380

Middle Eastern (MID) AF: 0.000174 AC: 1 AN: 5756

European-Non Finnish (NFE) AF: 0.000143 AC: 157 AN: 1100972

Other (OTH) AF: 0.000517 AC: 31 AN: 59992

GnomAD4 genome AF: 0.000237 AC: 36 AN: 151622 Hom.: 0 Cov.: 32 AF XY: 0.000256 AC XY: 19 AN XY: 74182

African (AFR) AF: 0.000169 AC: 7 AN: 41488

American (AMR) AF: 0.000329 AC: 5 AN: 15212

Ashkenazi Jewish (ASJ) AF: 0.00379 AC: 13 AN: 3428

East Asian (EAS) AF: 0.000192 AC: 1 AN: 5196

South Asian (SAS) AF: 0.00 AC: 0 AN: 4824

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: 0.000148 AC: 10 AN: 67554

Other (OTH) AF: 0.00 AC: 0 AN: 2094

Alfa AF: 0.000198 Hom.: 0

Bravo AF: 0.000264

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: reviewed by expert panel

Pathogenic	VUS	Benign	Condition
-	-	2	RASopathy (2)
-	-	1	MAP2K1-related disorder (1)
-	-	1	not provided (1)
-	-	1	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	1.5
DANN	Benign	0.40
PhyloP100		-0.32
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0

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: rs368800650; hg19: chr15-66782110;