rs1894292

chr4-73483441-G-A

Variant summary

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

The NM_001133.2(AFM):c.89-500G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.418 in 152,042 control chromosomes in the GnomAD database, including 13,849 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 0.42 (13849 hom., cov: 33)
• Consequence: AFM NM_001133.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.00700

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=-0.95).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.477 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
AFM	NM_001133.2	c.89-500G>A		intron_variant		ENST00000226355.5
AFM	XM_017007842.3	c.89-500G>A		intron_variant
AFM	XM_017007843.3	c.89-500G>A		intron_variant
AFM	XM_017007844.3	c.89-500G>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
AFM	ENST00000226355.5	c.89-500G>A		intron_variant		1	NM_001133.2	P1

Frequencies

GnomAD3 genomes AF: 0.419 AC: 63593 AN: 151924 Hom.: 13851 Cov.: 33

Gnomad AFR AF: 0.321

Gnomad AMI AF: 0.436

Gnomad AMR AF: 0.354

Gnomad ASJ AF: 0.395

Gnomad EAS AF: 0.374

Gnomad SAS AF: 0.478

Gnomad FIN AF: 0.495

Gnomad MID AF: 0.430

Gnomad NFE AF: 0.482

Gnomad OTH AF: 0.393

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

GnomAD4 genome AF: 0.418 AC: 63600 AN: 152042 Hom.: 13849 Cov.: 33 AF XY: 0.417 AC XY: 30987 AN XY: 74350

Gnomad4 AFR AF: 0.320

Gnomad4 AMR AF: 0.354

Gnomad4 ASJ AF: 0.395

Gnomad4 EAS AF: 0.374

Gnomad4 SAS AF: 0.477

Gnomad4 FIN AF: 0.495

Gnomad4 NFE AF: 0.482

Gnomad4 OTH AF: 0.388

Alfa AF: 0.460 Hom.: 11286

Bravo AF: 0.402

Asia WGS AF: 0.391 AC: 1357 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
Cadd	Benign	0.16
Dann	Benign	0.33

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: rs1894292; hg19: chr4-74349158;