7-151186907-G-T

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BS1 BS2

The NM_001142459.2(ASB10):c.224C>A(p.Ala75Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00117 in 1,614,034 control chromosomes in the GnomAD database, including 20 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★). Synonymous variant affecting the same amino acid position (i.e. A75A) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.0058 (9 hom., cov: 32)
  • Exomes 𝑓: 0.00068 (11 hom.)
• Consequence: ASB10 NM_001142459.2 missense
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:2 O:1
• Conservation: PhyloP100: 1.60

Genes affected

ASB10 (HGNC:17185): (ankyrin repeat and SOCS box containing 10) The protein encoded by this gene is a member of the ankyrin repeat and SOCS box-containing (ASB) family of proteins. The SOCS box serves to couple suppressor of cytokine signaling (SOCS) proteins and their binding partners with the elongin B and C complex, possibly targeting them for degradation. Multiple alternatively spliced transcript variants have been described for this gene. [provided by RefSeq, Dec 2008]

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0035480857).
• BP6: Variant 7-151186907-G-T is Benign according to our data. Variant chr7-151186907-G-T is described in ClinVar as [Likely_benign]. Clinvar id is 99944.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00585 (891/152346) while in subpopulation AFR AF= 0.0196 (817/41580). AF 95% confidence interval is 0.0185. There are 9 homozygotes in gnomad4. There are 393 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
• BS2: High AC in GnomAd at 892 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ASB10	NM_001142459.2	c.224C>A	p.Ala75Glu	missense_variant	1/6	ENST00000420175.3
ASB10	NM_001142460.1	c.224C>A	p.Ala75Glu	missense_variant	1/5
ASB10	NM_080871.4	c.272-248C>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ASB10	ENST00000420175.3	c.224C>A	p.Ala75Glu	missense_variant	1/6	1	NM_001142459.2	P4
ASB10	ENST00000275838.5	c.224C>A	p.Ala75Glu	missense_variant	1/5	1
ASB10	ENST00000377867.7	c.272-248C>A		intron_variant		2		A1
ASB10	ENST00000415615.1	c.*268C>A		3_prime_UTR_variant, NMD_transcript_variant	2/3	4

Frequencies

GnomAD3 genomes AF: 0.00586 AC: 892 AN: 152228 Hom.: 10 Cov.: 32

Gnomad AFR AF: 0.0197

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00393

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.0000735

Gnomad OTH AF: 0.00382

GnomAD3 exomes AF: 0.00164 AC: 408 AN: 249188 Hom.: 4 AF XY: 0.00118 AC XY: 159 AN XY: 134958

Gnomad AFR exome AF: 0.0218

Gnomad AMR exome AF: 0.00110

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.0000980

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000895

Gnomad OTH exome AF: 0.000654

GnomAD4 exome AF: 0.000683 AC: 999 AN: 1461688 Hom.: 11 Cov.: 35 AF XY: 0.000593 AC XY: 431 AN XY: 727168

Gnomad4 AFR exome AF: 0.0236

Gnomad4 AMR exome AF: 0.00130

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000464

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000369

Gnomad4 OTH exome AF: 0.00161

GnomAD4 genome AF: 0.00585 AC: 891 AN: 152346 Hom.: 9 Cov.: 32 AF XY: 0.00528 AC XY: 393 AN XY: 74496

Gnomad4 AFR AF: 0.0196

Gnomad4 AMR AF: 0.00392

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000735

Gnomad4 OTH AF: 0.00378

Alfa AF: 0.000310 Hom.: 0

Bravo AF: 0.00723

ESP6500AA AF: 0.0166 AC: 73

ESP6500EA AF: 0.000349 AC: 3

ExAC AF: 0.00189 AC: 230

Asia WGS AF: 0.00144 AC: 5 AN: 3478

EpiCase AF: 0.00

EpiControl AF: 0.000296

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:2 Other:1

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Likely benign, criteria provided, single submitter	clinical testing	GeneDx	Nov 11, 2020	- -
Benign, criteria provided, single submitter	clinical testing	Invitae	Nov 10, 2023	- -

Glaucoma 1, open angle, F Other:1

not provided, no classification provided

literature only

Casey Eye Institute Glaucoma Genetics Lab

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.15
BayesDel_addAF	Benign	-0.56	T
BayesDel_noAF	Benign	-0.57
Cadd	Benign	15
Dann	Benign	0.66
Eigen	Benign	-0.57
Eigen_PC	Benign	-0.59
FATHMM_MKL	Benign	0.091	N
LIST_S2	Benign	0.68	T;T
MetaRNN	Benign	0.0035	T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.33	N;N
MutationTaster	Benign	1.0	N;N;N;N;N
PrimateAI	Benign	0.41	T
PROVEAN	Benign	0.40	N;N
REVEL	Benign	0.10
Sift	Benign	0.94	T;T
Sift4G	Benign	1.0	T;T
Polyphen		0.38	.;B
Vest4		0.28
MVP		0.23
MPC		0.10
ClinPred		0.016	T
GERP RS		4.4
Varity_R		0.12
gMVP		0.17

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: rs104886489; hg19: chr7-150883994;