9-38395931-C-T

Variant names:

• chr9-38395931-C-T
• rs2073477
• NM_000692.5:c.183C>T

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BA1

The NM_000692.5(ALDH1B1):​c.183C>T​(p.Thr61Thr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.153 in 1,613,694 control chromosomes in the GnomAD database, including 22,051 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.18 (2874 hom., cov: 32)
  • Exomes 𝑓: 0.15 (19177 hom.)
• Consequence: ALDH1B1 NM_000692.5 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -1.91

Genes affected

ALDH1B1 (HGNC:407): (aldehyde dehydrogenase 1 family member B1) This protein belongs to the aldehyde dehydrogenases family of proteins. Aldehyde dehydrogenase is the second enzyme of the major oxidative pathway of alcohol metabolism. This gene does not contain introns in the coding sequence. The variation of this locus may affect the development of alcohol-related problems. [provided by RefSeq, Jul 2008]

ACMG classification

Our verdict: Benign. The variant received -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BP6: Variant 9-38395931-C-T is Benign according to our data. Variant chr9-38395931-C-T is described in ClinVar as [Benign]. Clinvar id is 136359.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-1.91 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.368 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ALDH1B1	NM_000692.5	c.183C>T	p.Thr61Thr	synonymous_variant	Exon 2 of 2	ENST00000377698.4	NP_000683.3
ALDH1B1	XM_011517802.3	c.324C>T	p.Thr108Thr	synonymous_variant	Exon 2 of 2		XP_011516104.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ALDH1B1	ENST00000377698.4	c.183C>T	p.Thr61Thr	synonymous_variant	Exon 2 of 2	1	NM_000692.5	ENSP00000366927.3
ALDH1B1	ENST00000635162.1	c.183C>T	p.Thr61Thr	synonymous_variant	Exon 3 of 3	3		ENSP00000489053.1

Frequencies

GnomAD3 genomes AF: 0.181 AC: 27559 AN: 152096 Hom.: 2865 Cov.: 32

Gnomad AFR AF: 0.223

Gnomad AMI AF: 0.0921

Gnomad AMR AF: 0.245

Gnomad ASJ AF: 0.133

Gnomad EAS AF: 0.382

Gnomad SAS AF: 0.271

Gnomad FIN AF: 0.163

Gnomad MID AF: 0.149

Gnomad NFE AF: 0.126

Gnomad OTH AF: 0.174

GnomAD2 exomes AF: 0.198 AC: 49618 AN: 250902 AF XY: 0.192

Gnomad AFR exome AF: 0.229

Gnomad AMR exome AF: 0.330

Gnomad ASJ exome AF: 0.133

Gnomad EAS exome AF: 0.377

Gnomad FIN exome AF: 0.169

Gnomad NFE exome AF: 0.123

Gnomad OTH exome AF: 0.162

GnomAD4 exome AF: 0.150 AC: 219451 AN: 1461480 Hom.: 19177 Cov.: 32 AF XY: 0.152 AC XY: 110671 AN XY: 727068

Gnomad4 AFR exome AF: 0.224 AC: 7486 AN: 33480

Gnomad4 AMR exome AF: 0.319 AC: 14250 AN: 44724

Gnomad4 ASJ exome AF: 0.133 AC: 3487 AN: 26132

Gnomad4 EAS exome AF: 0.361 AC: 14345 AN: 39700

Gnomad4 SAS exome AF: 0.254 AC: 21897 AN: 86258

Gnomad4 FIN exome AF: 0.167 AC: 8876 AN: 53044

Gnomad4 NFE exome AF: 0.124 AC: 138298 AN: 1111982

Gnomad4 Remaining exome AF: 0.162 AC: 9791 AN: 60392

GnomAD4 genome AF: 0.181 AC: 27596 AN: 152214 Hom.: 2874 Cov.: 32 AF XY: 0.186 AC XY: 13816 AN XY: 74410

Gnomad4 AFR AF: 0.223 AC: 0.222998 AN: 0.222998

Gnomad4 AMR AF: 0.246 AC: 0.245916 AN: 0.245916

Gnomad4 ASJ AF: 0.133 AC: 0.133065 AN: 0.133065

Gnomad4 EAS AF: 0.382 AC: 0.381737 AN: 0.381737

Gnomad4 SAS AF: 0.270 AC: 0.270444 AN: 0.270444

Gnomad4 FIN AF: 0.163 AC: 0.16324 AN: 0.16324

Gnomad4 NFE AF: 0.126 AC: 0.126434 AN: 0.126434

Gnomad4 OTH AF: 0.179 AC: 0.178808 AN: 0.178808

Alfa AF: 0.146 Hom.: 5572

Bravo AF: 0.189

Asia WGS AF: 0.307 AC: 1064 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:1

Aug 29, 2013

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -

not provided Benign:1

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	0.034
DANN	Benign	0.66
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.6
Mutation Taster		=100/0	polymorphism (auto)

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: rs2073477; hg19: chr9-38395928; COSMIC: COSV66619181;