rs237057

Variant names:

• chr17-76737017-G-A
• rs237057
• NM_001195427.2:c.144C>T

Your query was ambiguous. Multiple possible variants found:

• chr17-76737017-G-A
• chr17-76737017-G-C

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6 BP7 BA1

The NM_001195427.2(SRSF2):​c.144C>T​(p.Asp48Asp) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.907 in 1,613,358 control chromosomes in the GnomAD database, including 670,295 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (no stars).

• Frequency:
  • Genomes: 𝑓 0.81 (52442 hom., cov: 35)
  • Exomes 𝑓: 0.92 (617853 hom.)
• Consequence: SRSF2 NM_001195427.2 synonymous
• Clinical Significance: Benign no assertion criteria provided B:1
• Conservation: PhyloP100: 2.15
• Publications: 30 publications found

Genes affected

SRSF2 (HGNC:10783): (serine and arginine rich splicing factor 2) The protein encoded by this gene is a member of the serine/arginine (SR)-rich family of pre-mRNA splicing factors, which constitute part of the spliceosome. Each of these factors contains an RNA recognition motif (RRM) for binding RNA and an RS domain for binding other proteins. The RS domain is rich in serine and arginine residues and facilitates interaction between different SR splicing factors. In addition to being critical for mRNA splicing, the SR proteins have also been shown to be involved in mRNA export from the nucleus and in translation. Two transcript variants encoding the same protein and one non-coding transcript variant have been found for this gene. In addition, a pseudogene of this gene has been found on chromosome 11. [provided by RefSeq, Sep 2010]

MFSD11 (HGNC:25458): (major facilitator superfamily domain containing 11) Predicted to be integral component of membrane. [provided by Alliance of Genome Resources, Apr 2022]

ENSG00000267168 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.48).
• BP6: Variant 17-76737017-G-A is Benign according to our data. Variant chr17-76737017-G-A is described in ClinVar as Benign. ClinVar VariationId is 3058855.Status of the report is no_assertion_criteria_provided, 0 stars.
• BP7: Synonymous conserved (PhyloP=2.15 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.925 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001195427.2. 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
	SRSF2	NM_001195427.2	MANE Select	c.144C>T	p.Asp48Asp	synonymous	Exon 1 of 3	NP_001182356.1	Q01130-1
	SRSF2	NM_003016.5		c.144C>T	p.Asp48Asp	synonymous	Exon 1 of 2	NP_003007.2
	MFSD11	NM_001242534.3		c.-146G>A		5_prime_UTR	Exon 1 of 14	NP_001229463.1	O43934-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SRSF2	ENST00000359995.10	TSL:1 MANE Select	c.144C>T	p.Asp48Asp	synonymous	Exon 1 of 3	ENSP00000353089.5	Q01130-1
	SRSF2	ENST00000392485.2	TSL:1	c.144C>T	p.Asp48Asp	synonymous	Exon 1 of 2	ENSP00000376276.2	Q01130-1
	MFSD11	ENST00000621483.4	TSL:1	c.-146G>A		5_prime_UTR	Exon 1 of 14	ENSP00000485005.1	O43934-1

Frequencies

GnomAD3 genomes AF: 0.809 AC: 123008 AN: 152112 Hom.: 52437 Cov.: 35

Gnomad AFR AF: 0.511

Gnomad AMI AF: 0.995

Gnomad AMR AF: 0.887

Gnomad ASJ AF: 0.958

Gnomad EAS AF: 0.920

Gnomad SAS AF: 0.919

Gnomad FIN AF: 0.894

Gnomad MID AF: 0.892

Gnomad NFE AF: 0.931

Gnomad OTH AF: 0.838

GnomAD2 exomes AF: 0.895 AC: 222037 AN: 248222 AF XY: 0.903

Gnomad AFR exome AF: 0.498

Gnomad AMR exome AF: 0.912

Gnomad ASJ exome AF: 0.952

Gnomad EAS exome AF: 0.923

Gnomad FIN exome AF: 0.891

Gnomad NFE exome AF: 0.929

Gnomad OTH exome AF: 0.917

GnomAD4 exome AF: 0.917 AC: 1340100 AN: 1461128 Hom.: 617853 Cov.: 85 AF XY: 0.919 AC XY: 667668 AN XY: 726890

African (AFR) AF: 0.502 AC: 16804 AN: 33468

American (AMR) AF: 0.910 AC: 40698 AN: 44700

Ashkenazi Jewish (ASJ) AF: 0.951 AC: 24822 AN: 26114

East Asian (EAS) AF: 0.910 AC: 36117 AN: 39690

South Asian (SAS) AF: 0.916 AC: 79037 AN: 86244

European-Finnish (FIN) AF: 0.891 AC: 47116 AN: 52876

Middle Eastern (MID) AF: 0.889 AC: 5126 AN: 5766

European-Non Finnish (NFE) AF: 0.932 AC: 1036073 AN: 1111888

Other (OTH) AF: 0.899 AC: 54307 AN: 60382

GnomAD4 genome AF: 0.808 AC: 123053 AN: 152230 Hom.: 52442 Cov.: 35 AF XY: 0.811 AC XY: 60362 AN XY: 74438

African (AFR) AF: 0.511 AC: 21194 AN: 41506

American (AMR) AF: 0.887 AC: 13578 AN: 15304

Ashkenazi Jewish (ASJ) AF: 0.958 AC: 3326 AN: 3472

East Asian (EAS) AF: 0.920 AC: 4761 AN: 5174

South Asian (SAS) AF: 0.919 AC: 4443 AN: 4832

European-Finnish (FIN) AF: 0.894 AC: 9496 AN: 10620

Middle Eastern (MID) AF: 0.888 AC: 261 AN: 294

European-Non Finnish (NFE) AF: 0.931 AC: 63311 AN: 68002

Other (OTH) AF: 0.840 AC: 1776 AN: 2114

Alfa AF: 0.889 Hom.: 84309

Bravo AF: 0.793

Asia WGS AF: 0.882 AC: 3066 AN: 3478

EpiCase AF: 0.935

EpiControl AF: 0.933

ClinVar

ClinVar submissions

Significance: Benign

Revision: no assertion criteria provided

Pathogenic	VUS	Benign	Condition
-	-	1	SRSF2-related disorder (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.48
CADD	Benign	13
DANN	Uncertain	0.98
PhyloP100		2.1
PromoterAI		0.058	Neutral
Mutation Taster		=93/7	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: rs237057; hg19: chr17-74733099; COSMIC: COSV57970090; COSMIC: COSV57970090;