12-119016842-C-G

Position:

• chr12-119016842-C-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_194286.4(SRRM4):​c.131+34829C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.888 in 152,316 control chromosomes in the GnomAD database, including 60,297 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 0.89 (60297 hom., cov: 33)
• Consequence: SRRM4 NM_194286.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0190

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.97).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.918 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SRRM4	NM_194286.4	c.131+34829C>G		intron_variant		ENST00000267260.5	NP_919262.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SRRM4	ENST00000267260.5	c.131+34829C>G		intron_variant		1	NM_194286.4	ENSP00000267260	P1

Frequencies

GnomAD3 genomes AF: 0.888 AC: 135162 AN: 152198 Hom.: 60240 Cov.: 33

Gnomad AFR AF: 0.926

Gnomad AMI AF: 0.919

Gnomad AMR AF: 0.852

Gnomad ASJ AF: 0.976

Gnomad EAS AF: 0.716

Gnomad SAS AF: 0.750

Gnomad FIN AF: 0.863

Gnomad MID AF: 0.956

Gnomad NFE AF: 0.895

Gnomad OTH AF: 0.901

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

GnomAD4 genome AF: 0.888 AC: 135279 AN: 152316 Hom.: 60297 Cov.: 33 AF XY: 0.883 AC XY: 65740 AN XY: 74482

Gnomad4 AFR AF: 0.926

Gnomad4 AMR AF: 0.852

Gnomad4 ASJ AF: 0.976

Gnomad4 EAS AF: 0.716

Gnomad4 SAS AF: 0.750

Gnomad4 FIN AF: 0.863

Gnomad4 NFE AF: 0.894

Gnomad4 OTH AF: 0.902

Alfa AF: 0.889 Hom.: 7480

Bravo AF: 0.889

Asia WGS AF: 0.780 AC: 2713 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	1.9
DANN	Benign	0.27

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: rs7138083; hg19: chr12-119454647;