rs7302554

chr12-119092619-A-Gchr12-119092619-A-T

Variant summary

Our verdict is Benign. Variant got -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

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]

(HGNC:):

ACMG classification

Verdict is Benign. Variant got -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/exons	MANE	UniProt
SRRM4	NM_194286.4	c.132-9617A>G		intron_variant		ENST00000267260.5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SRRM4	ENST00000267260.5	c.132-9617A>G		intron_variant		1	NM_194286.4	P1
	ENST00000537730.1	n.76-22940T>C		intron_variant, non_coding_transcript_variant		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

Gnomad4 AFR AF: 0.780

Gnomad4 AMR AF: 0.733

Gnomad4 ASJ AF: 0.702

Gnomad4 EAS AF: 0.487

Gnomad4 SAS AF: 0.694

Gnomad4 FIN AF: 0.648

Gnomad4 NFE AF: 0.660

Gnomad4 OTH AF: 0.709

Alfa AF: 0.673 Hom.: 71041

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

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

Publications

LitVar

Other links and lift over

dbSNP: rs7302554; hg19: chr12-119530424;