2-38750470-A-G

Variant names:

• chr2-38750470-A-G
• rs3134628
• NM_001031684.3:c.29-276T>C

Variant summary

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

The NM_001031684.3(SRSF7):​c.29-276T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.711 in 151,296 control chromosomes in the GnomAD database, including 38,425 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 0.71 (38425 hom., cov: 27)
• Consequence: SRSF7 NM_001031684.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.10
• Publications: 3 publications found

Genes affected

SRSF7 (HGNC:10789): (serine and arginine rich splicing factor 7) 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 N-terminal RNA recognition motif (RRM) for binding RNA and a C-terminal 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. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, May 2018]

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.858 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001031684.3. 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
	SRSF7	NM_001031684.3	MANE Select	c.29-276T>C		intron	N/A	NP_001026854.1	Q16629-1
	SRSF7	NM_001363802.1		c.29-276T>C		intron	N/A	NP_001350731.1	C9JAB2
	SRSF7	NM_001195446.2		c.29-276T>C		intron	N/A	NP_001182375.1	Q16629-4

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SRSF7	ENST00000313117.11	TSL:1 MANE Select	c.29-276T>C		intron	N/A	ENSP00000325905.6	Q16629-1
	SRSF7	ENST00000926871.1		c.29-276T>C		intron	N/A	ENSP00000596930.1
	SRSF7	ENST00000409276.5	TSL:5	c.29-276T>C		intron	N/A	ENSP00000386806.1	C9JAB2

Frequencies

GnomAD3 genomes AF: 0.711 AC: 107462 AN: 151184 Hom.: 38413 Cov.: 27

Gnomad AFR AF: 0.717

Gnomad AMI AF: 0.798

Gnomad AMR AF: 0.695

Gnomad ASJ AF: 0.780

Gnomad EAS AF: 0.880

Gnomad SAS AF: 0.750

Gnomad FIN AF: 0.665

Gnomad MID AF: 0.793

Gnomad NFE AF: 0.697

Gnomad OTH AF: 0.731

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

GnomAD4 genome AF: 0.711 AC: 107517 AN: 151296 Hom.: 38425 Cov.: 27 AF XY: 0.713 AC XY: 52646 AN XY: 73882

African (AFR) AF: 0.717 AC: 29580 AN: 41278

American (AMR) AF: 0.694 AC: 10573 AN: 15228

Ashkenazi Jewish (ASJ) AF: 0.780 AC: 2704 AN: 3466

East Asian (EAS) AF: 0.880 AC: 4441 AN: 5048

South Asian (SAS) AF: 0.748 AC: 3576 AN: 4780

European-Finnish (FIN) AF: 0.665 AC: 6932 AN: 10430

Middle Eastern (MID) AF: 0.805 AC: 235 AN: 292

European-Non Finnish (NFE) AF: 0.697 AC: 47205 AN: 67756

Other (OTH) AF: 0.733 AC: 1548 AN: 2112

Alfa AF: 0.701 Hom.: 39402

Bravo AF: 0.712

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	5.0
DANN	Benign	0.51
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: rs3134628; hg19: chr2-38977612;