rs4646871

Variant names:

• chr6-134944479-G-A
• rs4646871
• NM_022568.4:c.139-513C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_022568.4(ALDH8A1):​c.139-513C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.489 in 151,996 control chromosomes in the GnomAD database, including 18,584 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.49 (18584 hom., cov: 32)
• Consequence: ALDH8A1 NM_022568.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.185
• Publications: 14 publications found

Genes affected

ALDH8A1 (HGNC:15471): (aldehyde dehydrogenase 8 family member A1) This gene encodes a member of the aldehyde dehydrogenase family of proteins. The encoded protein has been implicated in the synthesis of 9-cis-retinoic acid and in the breakdown of the amino acid tryptophan. This enzyme converts 9-cis-retinal into the retinoid X receptor ligand 9-cis-retinoic acid, and has approximately 40-fold higher activity with 9-cis-retinal than with all-trans-retinal. In addition, this enzyme has been shown to catalyze the conversion of 2-aminomuconic semialdehyde to 2-aminomuconate in the kynurenine pathway of tryptophan catabolism. [provided by RefSeq, Jul 2018]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.98).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.589 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ALDH8A1	NM_022568.4	c.139-513C>T		intron_variant	Intron 1 of 6	ENST00000265605.7	NP_072090.1
ALDH8A1	NM_001193480.2	c.139-513C>T		intron_variant	Intron 1 of 5		NP_001180409.1
ALDH8A1	NM_170771.3	c.139-513C>T		intron_variant	Intron 1 of 5		NP_739577.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ALDH8A1	ENST00000265605.7	c.139-513C>T		intron_variant	Intron 1 of 6	1	NM_022568.4	ENSP00000265605.2

Frequencies

GnomAD3 genomes AF: 0.489 AC: 74224 AN: 151878 Hom.: 18549 Cov.: 32

Gnomad AFR AF: 0.595

Gnomad AMI AF: 0.370

Gnomad AMR AF: 0.460

Gnomad ASJ AF: 0.432

Gnomad EAS AF: 0.514

Gnomad SAS AF: 0.511

Gnomad FIN AF: 0.493

Gnomad MID AF: 0.367

Gnomad NFE AF: 0.432

Gnomad OTH AF: 0.449

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.489 AC: 74307 AN: 151996 Hom.: 18584 Cov.: 32 AF XY: 0.489 AC XY: 36355 AN XY: 74284

African (AFR) AF: 0.596 AC: 24679 AN: 41440

American (AMR) AF: 0.461 AC: 7041 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.432 AC: 1499 AN: 3470

East Asian (EAS) AF: 0.514 AC: 2654 AN: 5166

South Asian (SAS) AF: 0.511 AC: 2459 AN: 4810

European-Finnish (FIN) AF: 0.493 AC: 5199 AN: 10550

Middle Eastern (MID) AF: 0.367 AC: 108 AN: 294

European-Non Finnish (NFE) AF: 0.432 AC: 29384 AN: 67970

Other (OTH) AF: 0.449 AC: 947 AN: 2110

Alfa AF: 0.446 Hom.: 26142

Bravo AF: 0.491

Asia WGS AF: 0.533 AC: 1853 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
CADD	Benign	1.3
DANN	Benign	0.34
PhyloP100		-0.18
PromoterAI		0.029	Neutral
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

Other links and lift over

dbSNP: rs4646871; hg19: chr6-135265617; COSMIC: COSV55640846; COSMIC: COSV55640846;