17-78364457-A-G

Variant summary

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

The NR_110847.1(SOCS3-DT):n.405+1706A>G variant causes a intron, non coding transcript change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.538 in 151,994 control chromosomes in the GnomAD database, including 23,938 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 0.54 (23935 hom., cov: 32)
  • Exomes 𝑓: 0.56 (3 hom.)
• Consequence: SOCS3-DT NR_110847.1 intron, non_coding_transcript
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.19

Genes affected

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

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.95).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.653 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SOCS3-DT	NR_110847.1	n.405+1706A>G		intron_variant, non_coding_transcript_variant
SOCS3-DT	NR_110845.1	n.462-40A>G		intron_variant, non_coding_transcript_variant
SOCS3-DT	NR_110846.1	n.139-40A>G		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SOCS3-DT	ENST00000592569.1	n.400+1706A>G		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes AF: 0.538 AC: 81683 AN: 151860 Hom.: 23940 Cov.: 32

Gnomad AFR AF: 0.342

Gnomad AMI AF: 0.710

Gnomad AMR AF: 0.582

Gnomad ASJ AF: 0.558

Gnomad EAS AF: 0.0985

Gnomad SAS AF: 0.536

Gnomad FIN AF: 0.668

Gnomad MID AF: 0.472

Gnomad NFE AF: 0.658

Gnomad OTH AF: 0.529

GnomAD4 exome AF: 0.563 AC: 9 AN: 16 Hom.: 3 Cov.: 0 AF XY: 0.571 AC XY: 8 AN XY: 14

Gnomad4 AFR exome AF: 1.00

Gnomad4 NFE exome AF: 0.500

Gnomad4 OTH exome AF: 0.500

GnomAD4 genome AF: 0.538 AC: 81697 AN: 151978 Hom.: 23935 Cov.: 32 AF XY: 0.538 AC XY: 39910 AN XY: 74246

Gnomad4 AFR AF: 0.342

Gnomad4 AMR AF: 0.582

Gnomad4 ASJ AF: 0.558

Gnomad4 EAS AF: 0.0985

Gnomad4 SAS AF: 0.536

Gnomad4 FIN AF: 0.668

Gnomad4 NFE AF: 0.658

Gnomad4 OTH AF: 0.524

Alfa AF: 0.625 Hom.: 42163

Bravo AF: 0.516

Asia WGS AF: 0.353 AC: 1230 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
Cadd	Benign	0.042
Dann	Benign	0.59

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs4969170; hg19: chr17-76360538;