chr11-67665486-C-T

Variant names:

• chr11-67665486-C-T
• rs140215620
• NM_001393402.2:c.505G>A

Variant summary

Our verdict is Likely benign. The variant received -6 ACMG points: 0P and 6B. BP4_Strong BP6_Moderate

The NM_001393402.2(ALDH3B2):​c.505G>A​(p.Val169Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000164 in 1,614,066 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.00016 (0 hom., cov: 32)
  • Exomes 𝑓: 0.00016 (0 hom.)
• Consequence: ALDH3B2 NM_001393402.2 missense
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -1.42
• Publications: 3 publications found

Genes affected

ALDH3B2 (HGNC:411): (aldehyde dehydrogenase 3 family member B2) This gene encodes a member of the aldehyde dehydrogenase family, a group of isozymes that may play a major role in the detoxification of aldehydes generated by alcohol metabolism and lipid peroxidation. The gene of this particular family member is over 10 kb in length. Altered methylation patterns at this locus have been observed in spermatozoa derived from patients exhibiting reduced fecundity. [provided by RefSeq, Aug 2017]

ACMG classification

Our verdict: Likely_benign. The variant received -6 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.020133793).
• BP6: Variant 11-67665486-C-T is Benign according to our data. Variant chr11-67665486-C-T is described in ClinVar as Likely_benign. ClinVar VariationId is 2385977.Status of the report is criteria_provided_single_submitter, 1 stars.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001393402.2. 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
	ALDH3B2	NM_001393402.2	MANE Select	c.505G>A	p.Val169Ile	missense	Exon 7 of 10	NP_001380331.1	P48448
	ALDH3B2	NM_001031615.3		c.505G>A	p.Val169Ile	missense	Exon 7 of 10	NP_001026786.3	P48448
	ALDH3B2	NM_001354345.3		c.505G>A	p.Val169Ile	missense	Exon 8 of 11	NP_001341274.2	P48448

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ALDH3B2	ENST00000673966.2	MANE Select	c.505G>A	p.Val169Ile	missense	Exon 7 of 10	ENSP00000501254.1	P48448
	ALDH3B2	ENST00000530069.6	TSL:1	c.505G>A	p.Val169Ile	missense	Exon 7 of 10	ENSP00000431595.1	P48448
	ALDH3B2	ENST00000349015.7	TSL:5	c.505G>A	p.Val169Ile	missense	Exon 7 of 10	ENSP00000255084.3	P48448

Frequencies

GnomAD3 genomes AF: 0.000164 AC: 25 AN: 152140 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.0000483

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000655

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000620

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000265

Gnomad OTH AF: 0.000478

GnomAD2 exomes AF: 0.000271 AC: 68 AN: 251370 AF XY: 0.000287

Gnomad AFR exome AF: 0.0000615

Gnomad AMR exome AF: 0.000145

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.0000544

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000299

Gnomad OTH exome AF: 0.000652

GnomAD4 exome AF: 0.000164 AC: 240 AN: 1461808 Hom.: 0 Cov.: 36 AF XY: 0.000176 AC XY: 128 AN XY: 727218

African (AFR) AF: 0.0000299 AC: 1 AN: 33478

American (AMR) AF: 0.0000895 AC: 4 AN: 44716

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26130

East Asian (EAS) AF: 0.0000504 AC: 2 AN: 39700

South Asian (SAS) AF: 0.000591 AC: 51 AN: 86250

European-Finnish (FIN) AF: 0.000187 AC: 10 AN: 53404

Middle Eastern (MID) AF: 0.000174 AC: 1 AN: 5740

European-Non Finnish (NFE) AF: 0.000137 AC: 152 AN: 1112000

Other (OTH) AF: 0.000315 AC: 19 AN: 60390

GnomAD4 genome AF: 0.000164 AC: 25 AN: 152258 Hom.: 0 Cov.: 32 AF XY: 0.000134 AC XY: 10 AN XY: 74444

African (AFR) AF: 0.0000482 AC: 2 AN: 41536

American (AMR) AF: 0.0000654 AC: 1 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5176

South Asian (SAS) AF: 0.000621 AC: 3 AN: 4832

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10626

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.000265 AC: 18 AN: 68004

Other (OTH) AF: 0.000473 AC: 1 AN: 2116

Alfa AF: 0.000265 Hom.: 0

Bravo AF: 0.000121

TwinsUK AF: 0.000270 AC: 1

ALSPAC AF: 0.00 AC: 0

ESP6500AA AF: 0.000227 AC: 1

ESP6500EA AF: 0.000116 AC: 1

ExAC AF: 0.000371 AC: 45

Asia WGS AF: 0.000289 AC: 1 AN: 3478

EpiCase AF: 0.000218

EpiControl AF: 0.000178

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.080
BayesDel_addAF	Benign	-0.49	T
BayesDel_noAF	Benign	-0.57
CADD	Benign	0.021
DANN	Benign	0.88
DEOGEN2	Benign	0.046	T
Eigen	Benign	-2.0
Eigen_PC	Benign	-2.0
FATHMM_MKL	Benign	0.19	N
LIST_S2	Benign	0.68	T
M_CAP	Uncertain	0.10	D
MetaRNN	Benign	0.020	T
MetaSVM	Benign	-0.91	T
MutationAssessor	Benign	0.57	N
PhyloP100		-1.4
PrimateAI	Benign	0.31	T
PROVEAN	Benign	0.19	N
REVEL	Benign	0.15
Sift	Benign	1.0	T
Sift4G	Benign	0.85	T
Polyphen		0.028	B
Vest4		0.090
MVP		0.27
MPC		0.17
ClinPred		0.021	T
GERP RS		-4.2
PromoterAI		0.022	Neutral
Varity_R		0.029
gMVP		0.31
Mutation Taster		=96/4	polymorphism

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

Other links and lift over

dbSNP: rs140215620; hg19: chr11-67432957;