rs1894292

Variant names:

• chr4-73483441-G-A
• rs1894292
• NM_001133.2:c.89-500G>A

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 45 publications found

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

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001133.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	AFM	NM_001133.2	MANE Select	c.89-500G>A		intron	N/A	NP_001124.1	P43652

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	AFM	ENST00000226355.5	TSL:1 MANE Select	c.89-500G>A		intron	N/A	ENSP00000226355.3	P43652
	AFM	ENST00000853605.1		c.89-500G>A		intron	N/A	ENSP00000523664.1
	AFM	ENST00000853610.1		c.89-500G>A		intron	N/A	ENSP00000523669.1

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

African (AFR) AF: 0.320 AC: 13280 AN: 41454

American (AMR) AF: 0.354 AC: 5408 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.395 AC: 1370 AN: 3472

East Asian (EAS) AF: 0.374 AC: 1935 AN: 5174

South Asian (SAS) AF: 0.477 AC: 2298 AN: 4822

European-Finnish (FIN) AF: 0.495 AC: 5234 AN: 10566

Middle Eastern (MID) AF: 0.432 AC: 127 AN: 294

European-Non Finnish (NFE) AF: 0.482 AC: 32731 AN: 67952

Other (OTH) AF: 0.388 AC: 820 AN: 2114

Alfa AF: 0.454 Hom.: 40690

Bravo AF: 0.402

Asia WGS AF: 0.391 AC: 1357 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	0.16
DANN	Benign	0.33
PhyloP100		-0.0070
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: rs1894292; hg19: chr4-74349158;