15-100629606-C-T

Variant names:

• chr15-100629606-C-T
• rs112822635
• NM_198243.3:c.381C>T

Variant summary

Our verdict is Benign. Variant got -11 ACMG points: 0P and 11B. BP4_Strong BP6_Moderate BP7 BS2

The NM_198243.3(ASB7):​c.381C>T​(p.Tyr127Tyr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000524 in 1,614,186 control chromosomes in the GnomAD database, including 6 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.0027 (1 hom., cov: 33)
  • Exomes 𝑓: 0.00030 (5 hom.)
• Consequence: ASB7 NM_198243.3 synonymous
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.981

Genes affected

ASB7 (HGNC:17182): (ankyrin repeat and SOCS box containing 7) The protein encoded by this gene belongs to a family of ankyrin repeat proteins that, along with four other protein families, contains a C-terminal SOCS box motif. Growing evidence suggests that the SOCS box acts as a bridge between specific substrate-binding domains and the more generic proteins that comprise a large family of E3 ubiquitin protein ligases. In this way, SOCS box containing proteins may regulate protein turnover by targeting proteins for polyubiquination and, therefore, for proteasome-mediated degradation. Two alternative transcripts encoding different isoforms have been described. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -11 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.52).
• BP6: Variant 15-100629606-C-T is Benign according to our data. Variant chr15-100629606-C-T is described in ClinVar as [Benign]. Clinvar id is 724645.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=-0.981 with no splicing effect.
• BS2: High AC in GnomAd4 at 412 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ASB7	NM_198243.3	c.381C>T	p.Tyr127Tyr	synonymous_variant	Exon 5 of 6	ENST00000332783.12	NP_937886.1
ASB7	NM_024708.4	c.381C>T	p.Tyr127Tyr	synonymous_variant	Exon 5 of 5		NP_078984.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ASB7	ENST00000332783.12	c.381C>T	p.Tyr127Tyr	synonymous_variant	Exon 5 of 6	1	NM_198243.3	ENSP00000328327.8
ASB7	ENST00000343276.4	c.381C>T	p.Tyr127Tyr	synonymous_variant	Exon 5 of 5	1		ENSP00000339819.4
ASB7	ENST00000558747.5	c.211+17179C>T		intron_variant	Intron 4 of 4	5		ENSP00000453626.1

Frequencies

GnomAD3 genomes AF: 0.00270 AC: 411 AN: 152208 Hom.: 1 Cov.: 33

Gnomad AFR AF: 0.00953

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000589

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: 0.0000588

Gnomad OTH AF: 0.000478

GnomAD3 exomes AF: 0.000673 AC: 169 AN: 251140 Hom.: 3 AF XY: 0.000560 AC XY: 76 AN XY: 135758

Gnomad AFR exome AF: 0.00938

Gnomad AMR exome AF: 0.000231

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.0000544

Gnomad SAS exome AF: 0.0000327

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000441

Gnomad OTH exome AF: 0.000326

GnomAD4 exome AF: 0.000297 AC: 434 AN: 1461860 Hom.: 5 Cov.: 32 AF XY: 0.000257 AC XY: 187 AN XY: 727230

Gnomad4 AFR exome AF: 0.00968

Gnomad4 AMR exome AF: 0.000425

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.0000756

Gnomad4 SAS exome AF: 0.000162

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000387

Gnomad4 OTH exome AF: 0.000447

GnomAD4 genome AF: 0.00270 AC: 412 AN: 152326 Hom.: 1 Cov.: 33 AF XY: 0.00258 AC XY: 192 AN XY: 74484

Gnomad4 AFR AF: 0.00953

Gnomad4 AMR AF: 0.000588

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.000385

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000588

Gnomad4 OTH AF: 0.000473

Alfa AF: 0.00146 Hom.: 0

Bravo AF: 0.00304

Asia WGS AF: 0.000577 AC: 2 AN: 3478

EpiCase AF: 0.000109

EpiControl AF: 0.00

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

May 16, 2018

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.52
CADD	Benign	4.0
DANN	Benign	0.64

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

Publications

LitVar

Other links and lift over

dbSNP: rs112822635; hg19: chr15-101169811; COSMIC: COSV100235093;