rs1894293

chr4-73486305-G-Achr4-73486305-G-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001133.2(AFM):c.482+232G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.611 in 152,006 control chromosomes in the GnomAD database, including 29,811 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 0.61 (29811 hom., cov: 31)
• Consequence: AFM NM_001133.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.112

Genes affected

AFM (HGNC:316): (afamin) This gene is a member of the albumin gene family, which is comprised of four genes that localize to chromosome 4 in a tandem arrangement. These four genes encode structurally-related serum transport proteins that are known to be evolutionarily related. The protein encoded by this gene is regulated developmentally, expressed in the liver and secreted into the bloodstream. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.718 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
AFM	NM_001133.2	c.482+232G>A		intron_variant		ENST00000226355.5
AFM	XM_017007842.3	c.482+232G>A		intron_variant
AFM	XM_017007843.3	c.482+232G>A		intron_variant
AFM	XM_017007844.3	c.482+232G>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
AFM	ENST00000226355.5	c.482+232G>A		intron_variant		1	NM_001133.2	P1

Frequencies

GnomAD3 genomes AF: 0.611 AC: 92846 AN: 151888 Hom.: 29815 Cov.: 31

Gnomad AFR AF: 0.418

Gnomad AMI AF: 0.647

Gnomad AMR AF: 0.545

Gnomad ASJ AF: 0.556

Gnomad EAS AF: 0.635

Gnomad SAS AF: 0.596

Gnomad FIN AF: 0.755

Gnomad MID AF: 0.579

Gnomad NFE AF: 0.724

Gnomad OTH AF: 0.579

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

GnomAD4 genome AF: 0.611 AC: 92863 AN: 152006 Hom.: 29811 Cov.: 31 AF XY: 0.610 AC XY: 45296 AN XY: 74300

Gnomad4 AFR AF: 0.418

Gnomad4 AMR AF: 0.545

Gnomad4 ASJ AF: 0.556

Gnomad4 EAS AF: 0.635

Gnomad4 SAS AF: 0.596

Gnomad4 FIN AF: 0.755

Gnomad4 NFE AF: 0.724

Gnomad4 OTH AF: 0.572

Alfa AF: 0.679 Hom.: 7063

Bravo AF: 0.588

Asia WGS AF: 0.568 AC: 1977 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
Cadd	Benign	5.0
Dann	Benign	0.25

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: rs1894293; hg19: chr4-74352022; COSMIC: COSV56919276;