chr4-73497565-T-A

Variant names:

• chr4-73497565-T-A
• NM_001133.2:c.1192-87T>A

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001133.2(AFM):​c.1192-87T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000164 in 608,820 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: not found (cov: 32)
  • Exomes 𝑓: 0.0000016 (0 hom.)
• Consequence: AFM NM_001133.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0960

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 Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
AFM	NM_001133.2	c.1192-87T>A		intron_variant	Intron 9 of 14	ENST00000226355.5	NP_001124.1
AFM	XM_017007842.3	c.1192-87T>A		intron_variant	Intron 9 of 12		XP_016863331.1
AFM	XM_017007843.3	c.1192-87T>A		intron_variant	Intron 9 of 10		XP_016863332.1
AFM	XM_017007844.3	c.1192-87T>A		intron_variant	Intron 9 of 10		XP_016863333.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
AFM	ENST00000226355.5	c.1192-87T>A		intron_variant	Intron 9 of 14	1	NM_001133.2	ENSP00000226355.3
AFM	ENST00000505794.1	n.319-87T>A		intron_variant	Intron 1 of 1	2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000164 AC: 1 AN: 608820 Hom.: 0 AF XY: 0.00000322 AC XY: 1 AN XY: 310992

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000223

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	4.2
DANN	Benign	0.70

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr4-74363282;