9-38396067-C-A

Variant names:

• chr9-38396067-C-A
• NM_000692.5:c.319C>A

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_000692.5(ALDH1B1):​c.319C>A​(p.Arg107Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,810 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 11/19 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R107L) has been classified as Likely benign.

• Frequency:
  • Genomes: not found (cov: 34)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: ALDH1B1 NM_000692.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.415

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

Verdict is Uncertain_significance. Variant got 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.2984766).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ALDH1B1	NM_000692.5	c.319C>A	p.Arg107Ser	missense_variant	Exon 2 of 2	ENST00000377698.4	NP_000683.3
ALDH1B1	XM_011517802.3	c.460C>A	p.Arg154Ser	missense_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.319C>A	p.Arg107Ser	missense_variant	Exon 2 of 2	1	NM_000692.5	ENSP00000366927.3
ALDH1B1	ENST00000635162.1	c.319C>A	p.Arg107Ser	missense_variant	Exon 3 of 3	3		ENSP00000489053.1

Frequencies

GnomAD3 genomes Cov.: 34

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461810 Hom.: 0 Cov.: 100 AF XY: 0.00000138 AC XY: 1 AN XY: 727204

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.0000166

GnomAD4 genome Cov.: 34

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.39
BayesDel_addAF	Benign	-0.051	T
BayesDel_noAF	Benign	-0.31
CADD	Benign	20
DANN	Uncertain	0.99
DEOGEN2	Benign	0.11	.;T
Eigen	Benign	-0.48
Eigen_PC	Benign	-0.40
FATHMM_MKL	Benign	0.41	N
LIST_S2	Benign	0.70	T;T
M_CAP	Uncertain	0.18	D
MetaRNN	Benign	0.30	T;T
MetaSVM	Benign	-0.87	T
PrimateAI	Benign	0.23	T
PROVEAN	Uncertain	-3.5	D;.
REVEL	Benign	0.25
Sift	Uncertain	0.0010	D;.
Sift4G	Uncertain	0.030	D;D
Vest4		0.37
MutPred		0.66		Loss of MoRF binding (P = 0.0121);Loss of MoRF binding (P = 0.0121);
MVP		0.45
MPC		0.21
ClinPred		0.95	D
GERP RS		1.6
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.6
gMVP		0.50

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr9-38396064;