rs4994934

Variant names:

• chr17-78368596-T-C
• rs4994934
• ENST00000592569.1:n.475-132T>C

Variant summary

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

The ENST00000592569.1(SOCS3-DT):​n.475-132T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.908 in 152,348 control chromosomes in the GnomAD database, including 62,870 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 0.91 (62814 hom., cov: 33)
  • Exomes 𝑓: 0.88 (56 hom.)
• Consequence: SOCS3-DT ENST00000592569.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.06
• Publications: 3 publications found

Genes affected

SOCS3-DT (HGNC:52799): (SOCS3 divergent transcript)

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.93).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.927 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000592569.1. 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
	SOCS3-DT	NR_110847.1		n.480-132T>C		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SOCS3-DT	ENST00000592569.1	TSL:3	n.475-132T>C		intron	N/A
	SOCS3-DT	ENST00000794147.1		n.660+1330T>C		intron	N/A
	SOCS3-DT	ENST00000794148.1		n.501+1330T>C		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.908 AC: 138039 AN: 152086 Hom.: 62770 Cov.: 33

Gnomad AFR AF: 0.914

Gnomad AMI AF: 0.932

Gnomad AMR AF: 0.901

Gnomad ASJ AF: 0.895

Gnomad EAS AF: 0.735

Gnomad SAS AF: 0.950

Gnomad FIN AF: 0.898

Gnomad MID AF: 0.927

Gnomad NFE AF: 0.917

Gnomad OTH AF: 0.903

GnomAD4 exome AF: 0.882 AC: 127 AN: 144 Hom.: 56 AF XY: 0.914 AC XY: 106 AN XY: 116

African (AFR) AF: 1.00 AC: 2 AN: 2

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AF: 1.00 AC: 2 AN: 2

East Asian (EAS) AF: 0.750 AC: 6 AN: 8

South Asian (SAS) AF: 1.00 AC: 6 AN: 6

European-Finnish (FIN) AF: 0.833 AC: 10 AN: 12

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.908 AC: 89 AN: 98

Other (OTH) AF: 0.750 AC: 12 AN: 16

GnomAD4 genome AF: 0.908 AC: 138142 AN: 152204 Hom.: 62814 Cov.: 33 AF XY: 0.908 AC XY: 67545 AN XY: 74396

African (AFR) AF: 0.914 AC: 37984 AN: 41538

American (AMR) AF: 0.901 AC: 13774 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.895 AC: 3109 AN: 3472

East Asian (EAS) AF: 0.735 AC: 3786 AN: 5154

South Asian (SAS) AF: 0.950 AC: 4579 AN: 4822

European-Finnish (FIN) AF: 0.898 AC: 9520 AN: 10598

Middle Eastern (MID) AF: 0.925 AC: 272 AN: 294

European-Non Finnish (NFE) AF: 0.917 AC: 62366 AN: 68016

Other (OTH) AF: 0.903 AC: 1908 AN: 2112

Alfa AF: 0.908 Hom.: 8104

Bravo AF: 0.904

Asia WGS AF: 0.863 AC: 3003 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	1.3
DANN	Benign	0.22
PhyloP100		-2.1

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs4994934;

hg19: chr17-76364677;