chr12-119092619-A-G

Variant names:

• chr12-119092619-A-G
• rs7302554
• NM_194286.4:c.132-9617A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_194286.4(SRRM4):​c.132-9617A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.696 in 151,736 control chromosomes in the GnomAD database, including 37,209 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.70 (37209 hom., cov: 30)
• Consequence: SRRM4 NM_194286.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.11
• Publications: 6 publications found

Genes affected

SRRM4 (HGNC:29389): (serine/arginine repetitive matrix 4) SRRM4 promotes alternative splicing and inclusion of neural-specific exons in target mRNAs (Calarco et al., 2009 [PubMed 19737518]).[supplied by OMIM, Oct 2009]

ENSG00000257095 (HGNC:58442):

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.773 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SRRM4	NM_194286.4	c.132-9617A>G		intron_variant	Intron 1 of 12	ENST00000267260.5	NP_919262.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SRRM4	ENST00000267260.5	c.132-9617A>G		intron_variant	Intron 1 of 12	1	NM_194286.4	ENSP00000267260.4
ENSG00000257095	ENST00000537730.1	n.76-22940T>C		intron_variant	Intron 1 of 3	3

Frequencies

GnomAD3 genomes AF: 0.696 AC: 105551 AN: 151616 Hom.: 37168 Cov.: 30

Gnomad AFR AF: 0.780

Gnomad AMI AF: 0.675

Gnomad AMR AF: 0.733

Gnomad ASJ AF: 0.702

Gnomad EAS AF: 0.488

Gnomad SAS AF: 0.695

Gnomad FIN AF: 0.648

Gnomad MID AF: 0.763

Gnomad NFE AF: 0.660

Gnomad OTH AF: 0.707

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.696 AC: 105645 AN: 151736 Hom.: 37209 Cov.: 30 AF XY: 0.695 AC XY: 51557 AN XY: 74158

African (AFR) AF: 0.780 AC: 32246 AN: 41338

American (AMR) AF: 0.733 AC: 11184 AN: 15262

Ashkenazi Jewish (ASJ) AF: 0.702 AC: 2434 AN: 3466

East Asian (EAS) AF: 0.487 AC: 2490 AN: 5110

South Asian (SAS) AF: 0.694 AC: 3333 AN: 4804

European-Finnish (FIN) AF: 0.648 AC: 6833 AN: 10538

Middle Eastern (MID) AF: 0.772 AC: 224 AN: 290

European-Non Finnish (NFE) AF: 0.660 AC: 44789 AN: 67906

Other (OTH) AF: 0.709 AC: 1499 AN: 2114

Alfa AF: 0.675 Hom.: 150388

Bravo AF: 0.706

Asia WGS AF: 0.599 AC: 2084 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.010
DANN	Benign	0.42
PhyloP100		-1.1
Mutation Taster		=100/0	polymorphism (auto)

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: rs7302554; hg19: chr12-119530424;