rs4646871

Positions:

• chr6-134944479-G-A

Variant summary

Our verdict is Benign. Variant got -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

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

Verdict is Benign. Variant got -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/exons	MANE	Protein	UniProt
ALDH8A1	NM_022568.4	c.139-513C>T		intron_variant		ENST00000265605.7	NP_072090.1
ALDH8A1	NM_001193480.2	c.139-513C>T		intron_variant			NP_001180409.1
ALDH8A1	NM_170771.3	c.139-513C>T		intron_variant			NP_739577.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ALDH8A1	ENST00000265605.7	c.139-513C>T		intron_variant		1	NM_022568.4	ENSP00000265605	P1
ALDH8A1	ENST00000367845.6	c.139-513C>T		intron_variant		1		ENSP00000356819
ALDH8A1	ENST00000349305.8	c.139-513C>T		intron_variant, NMD_transcript_variant		1		ENSP00000325473
ALDH8A1	ENST00000367847.2	c.139-513C>T		intron_variant		2		ENSP00000356821

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

Gnomad4 AFR AF: 0.596

Gnomad4 AMR AF: 0.461

Gnomad4 ASJ AF: 0.432

Gnomad4 EAS AF: 0.514

Gnomad4 SAS AF: 0.511

Gnomad4 FIN AF: 0.493

Gnomad4 NFE AF: 0.432

Gnomad4 OTH AF: 0.449

Alfa AF: 0.441 Hom.: 20063

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

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