chr11-67663252-C-T

Variant names:

• chr11-67663252-C-T
• rs140105486
• NM_001393402.2:c.1121G>A

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_001393402.2(ALDH3B2):​c.1121G>A​(p.Arg374His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00021 in 1,613,020 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.00022 (0 hom., cov: 34)
  • Exomes 𝑓: 0.00021 (0 hom.)
• Consequence: ALDH3B2 NM_001393402.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.624
• Publications: 2 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 -2 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.09203324).

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.1121G>A	p.Arg374His	missense	Exon 10 of 10	NP_001380331.1	P48448
	ALDH3B2	NM_001031615.3		c.1121G>A	p.Arg374His	missense	Exon 10 of 10	NP_001026786.3	P48448
	ALDH3B2	NM_001354345.3		c.1121G>A	p.Arg374His	missense	Exon 11 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.1121G>A	p.Arg374His	missense	Exon 10 of 10	ENSP00000501254.1	P48448
	ALDH3B2	ENST00000530069.6	TSL:1	c.1121G>A	p.Arg374His	missense	Exon 10 of 10	ENSP00000431595.1	P48448
	ALDH3B2	ENST00000349015.7	TSL:5	c.1121G>A	p.Arg374His	missense	Exon 10 of 10	ENSP00000255084.3	P48448

Frequencies

GnomAD3 genomes AF: 0.000223 AC: 34 AN: 152210 Hom.: 0 Cov.: 34

Gnomad AFR AF: 0.0000724

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000785

Gnomad ASJ AF: 0.000288

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000191

Gnomad OTH AF: 0.00191

GnomAD2 exomes AF: 0.000240 AC: 60 AN: 250004 AF XY: 0.000185

Gnomad AFR exome AF: 0.000123

Gnomad AMR exome AF: 0.000609

Gnomad ASJ exome AF: 0.000503

Gnomad EAS exome AF: 0.000109

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000213

Gnomad OTH exome AF: 0.000822

GnomAD4 exome AF: 0.000209 AC: 305 AN: 1460810 Hom.: 0 Cov.: 32 AF XY: 0.000187 AC XY: 136 AN XY: 726684

African (AFR) AF: 0.0000598 AC: 2 AN: 33472

American (AMR) AF: 0.000605 AC: 27 AN: 44652

Ashkenazi Jewish (ASJ) AF: 0.000538 AC: 14 AN: 26030

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

South Asian (SAS) AF: 0.00 AC: 0 AN: 86108

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53314

Middle Eastern (MID) AF: 0.000868 AC: 5 AN: 5762

European-Non Finnish (NFE) AF: 0.000190 AC: 211 AN: 1111422

Other (OTH) AF: 0.000729 AC: 44 AN: 60350

GnomAD4 genome AF: 0.000223 AC: 34 AN: 152210 Hom.: 0 Cov.: 34 AF XY: 0.000188 AC XY: 14 AN XY: 74348

African (AFR) AF: 0.0000724 AC: 3 AN: 41446

American (AMR) AF: 0.000785 AC: 12 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.000288 AC: 1 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5196

South Asian (SAS) AF: 0.000207 AC: 1 AN: 4830

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10620

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.000191 AC: 13 AN: 68042

Other (OTH) AF: 0.00191 AC: 4 AN: 2092

Alfa AF: 0.000221 Hom.: 0

Bravo AF: 0.000336

TwinsUK AF: 0.000539 AC: 2

ALSPAC AF: 0.00 AC: 0

ESP6500AA AF: 0.00 AC: 0

ESP6500EA AF: 0.000466 AC: 4

ExAC AF: 0.000198 AC: 24

EpiCase AF: 0.000273

EpiControl AF: 0.000356

ClinVar

ClinVar submissions

Significance: Uncertain significance

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	0.10
BayesDel_addAF	Benign	-0.41	T
BayesDel_noAF	Benign	-0.46
CADD	Benign	1.6
DANN	Uncertain	0.99
DEOGEN2	Benign	0.021	T
Eigen	Benign	-0.93
Eigen_PC	Benign	-1.1
FATHMM_MKL	Benign	0.089	N
LIST_S2	Benign	0.28	T
M_CAP	Benign	0.067	D
MetaRNN	Benign	0.092	T
MetaSVM	Benign	-0.73	T
MutationAssessor	Uncertain	2.0	M
PhyloP100		-0.62
PrimateAI	Benign	0.22	T
PROVEAN	Benign	-1.6	N
REVEL	Benign	0.25
Sift	Uncertain	0.023	D
Sift4G	Uncertain	0.024	D
Polyphen		0.98	D
Vest4		0.042
MVP		0.79
MPC		0.24
ClinPred		0.062	T
GERP RS		-3.2
Varity_R		0.036
gMVP		0.62
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: rs140105486; hg19: chr11-67430723;