chr4-99418439-A-G

Variant names:

• chr4-99418439-A-G
• rs1154456
• NM_000673.7:c.961+547T>C

Variant summary

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

The NM_000673.7(ADH7):​c.961+547T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.282 in 152,004 control chromosomes in the GnomAD database, including 6,582 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 0.28 (6582 hom., cov: 32)
• Consequence: ADH7 NM_000673.7 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.216
• Publications: 5 publications found

Genes affected

ADH7 (HGNC:256): (alcohol dehydrogenase 7 (class IV), mu or sigma polypeptide) This gene encodes class IV alcohol dehydrogenase 7 mu or sigma subunit, which is a member of the alcohol dehydrogenase family. Members of this family metabolize a wide variety of substrates, including ethanol, retinol, other aliphatic alcohols, hydroxysteroids, and lipid peroxidation products. The enzyme encoded by this gene is inefficient in ethanol oxidation, but is the most active as a retinol dehydrogenase; thus it may participate in the synthesis of retinoic acid, a hormone important for cellular differentiation. The expression of this gene is much more abundant in stomach than liver, thus differing from the other known gene family members. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Oct 2009]

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.94).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.363 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ADH7	NM_000673.7	c.961+547T>C		intron_variant	Intron 7 of 8	ENST00000437033.7	NP_000664.3
ADH7	NM_001166504.2	c.1021+547T>C		intron_variant	Intron 7 of 8		NP_001159976.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ADH7	ENST00000437033.7	c.961+547T>C		intron_variant	Intron 7 of 8	1	NM_000673.7	ENSP00000414254.2
ADH7	ENST00000209665.8	c.997+547T>C		intron_variant	Intron 7 of 8	1		ENSP00000209665.4
ADH7	ENST00000476959.5	c.1021+547T>C		intron_variant	Intron 7 of 8	2		ENSP00000420269.1
ADH7	ENST00000482593.5	c.790+547T>C		intron_variant	Intron 8 of 9	3		ENSP00000420613.1

Frequencies

GnomAD3 genomes AF: 0.282 AC: 42887 AN: 151886 Hom.: 6574 Cov.: 32

Gnomad AFR AF: 0.167

Gnomad AMI AF: 0.363

Gnomad AMR AF: 0.371

Gnomad ASJ AF: 0.242

Gnomad EAS AF: 0.271

Gnomad SAS AF: 0.307

Gnomad FIN AF: 0.303

Gnomad MID AF: 0.338

Gnomad NFE AF: 0.330

Gnomad OTH AF: 0.280

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

GnomAD4 genome AF: 0.282 AC: 42920 AN: 152004 Hom.: 6582 Cov.: 32 AF XY: 0.285 AC XY: 21173 AN XY: 74318

African (AFR) AF: 0.166 AC: 6908 AN: 41490

American (AMR) AF: 0.371 AC: 5661 AN: 15242

Ashkenazi Jewish (ASJ) AF: 0.242 AC: 841 AN: 3470

East Asian (EAS) AF: 0.271 AC: 1394 AN: 5150

South Asian (SAS) AF: 0.309 AC: 1488 AN: 4810

European-Finnish (FIN) AF: 0.303 AC: 3200 AN: 10560

Middle Eastern (MID) AF: 0.346 AC: 101 AN: 292

European-Non Finnish (NFE) AF: 0.330 AC: 22404 AN: 67972

Other (OTH) AF: 0.281 AC: 593 AN: 2108

Alfa AF: 0.321 Hom.: 13383

Bravo AF: 0.285

Asia WGS AF: 0.316 AC: 1101 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	2.9
DANN	Benign	0.76
PhyloP100		-0.22
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: rs1154456; hg19: chr4-100339596;