15-100629438-T-C

Variant names:

• chr15-100629438-T-C
• rs115563472
• NM_198243.3:c.213T>C

Variant summary

Our verdict is Benign. The variant received -19 ACMG points: 0P and 19B. BP4_Moderate BP6_Very_Strong BP7 BS1 BS2

The NM_198243.3(ASB7):​c.213T>C​(p.Ala71Ala) variant causes a splice region, synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00126 in 1,603,488 control chromosomes in the GnomAD database, including 26 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0067 (17 hom., cov: 33)
  • Exomes 𝑓: 0.00069 (9 hom.)
• Consequence: ASB7 NM_198243.3 splice_region, synonymous
• Scores: Splicing: ADA: 0.007173
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.541
• Publications: 1 publications found

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

Our verdict: Benign. The variant received -19 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.41).
• BP6: Variant 15-100629438-T-C is Benign according to our data. Variant chr15-100629438-T-C is described in ClinVar as Benign. ClinVar VariationId is 783722.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=0.541 with no splicing effect.
• BS1: Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.00673 (1025/152374) while in subpopulation AFR AF = 0.0235 (979/41584). AF 95% confidence interval is 0.0223. There are 17 homozygotes in GnomAd4. There are 511 alleles in the male GnomAd4 subpopulation. Median coverage is 33. This position passed quality control check.
• BS2: High AC in GnomAd4 at 1025 AD gene.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_198243.3. 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
	ASB7	NM_198243.3	MANE Select	c.213T>C	p.Ala71Ala	splice_region synonymous	Exon 5 of 6	NP_937886.1	Q9H672-1
	ASB7	NM_024708.4		c.213T>C	p.Ala71Ala	splice_region synonymous	Exon 5 of 5	NP_078984.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ASB7	ENST00000332783.12	TSL:1 MANE Select	c.213T>C	p.Ala71Ala	splice_region synonymous	Exon 5 of 6	ENSP00000328327.8	Q9H672-1
	ASB7	ENST00000343276.4	TSL:1	c.213T>C	p.Ala71Ala	splice_region synonymous	Exon 5 of 5	ENSP00000339819.4	Q9H672-2
	ASB7	ENST00000899523.1		c.213T>C	p.Ala71Ala	splice_region synonymous	Exon 4 of 5	ENSP00000569582.1

Frequencies

GnomAD3 genomes AF: 0.00672 AC: 1023 AN: 152256 Hom.: 17 Cov.: 33

Gnomad AFR AF: 0.0236

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00196

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.0000441

Gnomad OTH AF: 0.00526

GnomAD2 exomes AF: 0.00191 AC: 473 AN: 248092 AF XY: 0.00143

Gnomad AFR exome AF: 0.0253

Gnomad AMR exome AF: 0.00138

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000535

Gnomad OTH exome AF: 0.00200

GnomAD4 exome AF: 0.000690 AC: 1001 AN: 1451114 Hom.: 9 Cov.: 31 AF XY: 0.000614 AC XY: 442 AN XY: 720114

African (AFR) AF: 0.0243 AC: 805 AN: 33148

American (AMR) AF: 0.00134 AC: 59 AN: 44158

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25768

East Asian (EAS) AF: 0.00 AC: 0 AN: 39466

South Asian (SAS) AF: 0.0000117 AC: 1 AN: 85774

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53246

Middle Eastern (MID) AF: 0.00157 AC: 9 AN: 5726

European-Non Finnish (NFE) AF: 0.0000217 AC: 24 AN: 1104008

Other (OTH) AF: 0.00172 AC: 103 AN: 59820

GnomAD4 genome AF: 0.00673 AC: 1025 AN: 152374 Hom.: 17 Cov.: 33 AF XY: 0.00686 AC XY: 511 AN XY: 74518

African (AFR) AF: 0.0235 AC: 979 AN: 41584

American (AMR) AF: 0.00196 AC: 30 AN: 15304

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5192

South Asian (SAS) AF: 0.000207 AC: 1 AN: 4834

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10628

Middle Eastern (MID) AF: 0.00340 AC: 1 AN: 294

European-Non Finnish (NFE) AF: 0.0000441 AC: 3 AN: 68040

Other (OTH) AF: 0.00520 AC: 11 AN: 2114

Alfa AF: 0.00276 Hom.: 15

Bravo AF: 0.00753

Asia WGS AF: 0.00115 AC: 4 AN: 3478

EpiCase AF: 0.0000545

EpiControl AF: 0.0000593

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.41
CADD	Benign	8.8
DANN	Benign	0.81
PhyloP100		0.54
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Mutation Taster		=57/43	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.0072
dbscSNV1_RF	Benign	0.14
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: rs115563472; hg19: chr15-101169643;