chr1-70234746-C-G

Variant names:

• chr1-70234746-C-G
• rs372180100
• NM_001350605.2:c.498C>G

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BP4_Moderate BP6 BP7 BS2

The NM_001350605.2(SRSF11):​c.498C>G​(p.Ala166Ala) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000236 in 1,610,650 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (no stars).

• Frequency:
  • Genomes: 𝑓 0.000085 (0 hom., cov: 32)
  • Exomes 𝑓: 0.000017 (0 hom.)
• Consequence: SRSF11 NM_001350605.2 synonymous
• Clinical Significance: Likely benign no assertion criteria provided B:1
• Conservation: PhyloP100: 2.22
• Publications: 0 publications found

Genes affected

SRSF11 (HGNC:10782): (serine and arginine rich splicing factor 11) This gene encodes 54-kD nuclear protein that contains an arginine/serine-rich region similar to segments found in pre-mRNA splicing factors. Although the function of this protein is not yet known, structure and immunolocalization data suggest that it may play a role in pre-mRNA processing. Alternative splicing results in multiple transcript variants encoding different proteins. In addition, a pseudogene of this gene has been found on chromosome 12.[provided by RefSeq, Sep 2010]

ACMG classification

Our verdict: Benign. The variant received -8 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.24).
• BP6: Variant 1-70234746-C-G is Benign according to our data. Variant chr1-70234746-C-G is described in ClinVar as Likely_benign. ClinVar VariationId is 3040669.Status of the report is no_assertion_criteria_provided, 0 stars.
• BP7: Synonymous conserved (PhyloP=2.22 with no splicing effect.
• BS2: High AC in GnomAd4 at 13 AD gene.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001350605.2. 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
	SRSF11	NM_001350605.2	MANE Select	c.498C>G	p.Ala166Ala	synonymous	Exon 4 of 12	NP_001337534.1	Q05519-1
	SRSF11	NM_001394402.1		c.531C>G	p.Ala177Ala	synonymous	Exon 6 of 14	NP_001381331.1
	SRSF11	NM_001394403.1		c.531C>G	p.Ala177Ala	synonymous	Exon 5 of 13	NP_001381332.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SRSF11	ENST00000370949.2	TSL:1 MANE Select	c.498C>G	p.Ala166Ala	synonymous	Exon 4 of 12	ENSP00000359987.2	Q05519-1
	SRSF11	ENST00000395136.7	TSL:1	c.498C>G	p.Ala166Ala	synonymous	Exon 4 of 12	ENSP00000378568.3	Q5T760
	SRSF11	ENST00000370950.7	TSL:1	c.498C>G	p.Ala166Ala	synonymous	Exon 5 of 13	ENSP00000359988.3	Q05519-1

Frequencies

GnomAD3 genomes AF: 0.0000788 AC: 12 AN: 152192 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.000121

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000131

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000384

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00143

GnomAD2 exomes AF: 0.0000240 AC: 6 AN: 249956 AF XY: 0.0000222

Gnomad AFR exome AF: 0.000124

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.000110

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.000329

GnomAD4 exome AF: 0.0000171 AC: 25 AN: 1458340 Hom.: 0 Cov.: 30 AF XY: 0.0000207 AC XY: 15 AN XY: 725658

African (AFR) AF: 0.000120 AC: 4 AN: 33346

American (AMR) AF: 0.00 AC: 0 AN: 44394

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26060

East Asian (EAS) AF: 0.0000253 AC: 1 AN: 39528

South Asian (SAS) AF: 0.00 AC: 0 AN: 85900

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53320

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5402

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1110266

Other (OTH) AF: 0.000333 AC: 20 AN: 60124

GnomAD4 genome AF: 0.0000854 AC: 13 AN: 152310 Hom.: 0 Cov.: 32 AF XY: 0.0000806 AC XY: 6 AN XY: 74474

African (AFR) AF: 0.000120 AC: 5 AN: 41562

American (AMR) AF: 0.000131 AC: 2 AN: 15304

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.000385 AC: 2 AN: 5190

South Asian (SAS) AF: 0.00 AC: 0 AN: 4820

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10612

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 68032

Other (OTH) AF: 0.00189 AC: 4 AN: 2114

Alfa AF: 0.0000712 Hom.: 0

Bravo AF: 0.0000604

Asia WGS AF: 0.000866 AC: 3 AN: 3478

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: no assertion criteria provided

Pathogenic	VUS	Benign	Condition
-	-	1	SRSF11-related disorder (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.24
CADD	Benign	14
DANN	Benign	0.71
PhyloP100		2.2
RBP_binding_hub_radar		1.1
RBP_regulation_power_radar		2.8
Mutation Taster		=91/9	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
Splicevardb		2.0
SpliceAI score (max)		0.010		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: rs372180100; hg19: chr1-70700429;