4-73497565-T-C

Position:

• chr4-73497565-T-C

Variant summary

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

The NM_001133.2(AFM):​c.1192-87T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.244 in 759,300 control chromosomes in the GnomAD database, including 23,876 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 0.22 (4233 hom., cov: 32)
  • Exomes 𝑓: 0.25 (19643 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 Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.325 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
AFM	NM_001133.2	c.1192-87T>C		intron_variant		ENST00000226355.5	NP_001124.1
AFM	XM_017007842.3	c.1192-87T>C		intron_variant			XP_016863331.1
AFM	XM_017007843.3	c.1192-87T>C		intron_variant			XP_016863332.1
AFM	XM_017007844.3	c.1192-87T>C		intron_variant			XP_016863333.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
AFM	ENST00000226355.5	c.1192-87T>C		intron_variant		1	NM_001133.2	ENSP00000226355	P1
AFM	ENST00000505794.1	n.319-87T>C		intron_variant, non_coding_transcript_variant		2

Frequencies

GnomAD3 genomes AF: 0.224 AC: 33983 AN: 151996 Hom.: 4237 Cov.: 32

Gnomad AFR AF: 0.125

Gnomad AMI AF: 0.282

Gnomad AMR AF: 0.333

Gnomad ASJ AF: 0.323

Gnomad EAS AF: 0.325

Gnomad SAS AF: 0.296

Gnomad FIN AF: 0.231

Gnomad MID AF: 0.320

Gnomad NFE AF: 0.238

Gnomad OTH AF: 0.251

GnomAD4 exome AF: 0.249 AC: 151333 AN: 607186 Hom.: 19643 AF XY: 0.250 AC XY: 77483 AN XY: 310166

Gnomad4 AFR exome AF: 0.123

Gnomad4 AMR exome AF: 0.331

Gnomad4 ASJ exome AF: 0.329

Gnomad4 EAS exome AF: 0.331

Gnomad4 SAS exome AF: 0.289

Gnomad4 FIN exome AF: 0.234

Gnomad4 NFE exome AF: 0.241

Gnomad4 OTH exome AF: 0.260

GnomAD4 genome AF: 0.223 AC: 33984 AN: 152114 Hom.: 4233 Cov.: 32 AF XY: 0.228 AC XY: 16952 AN XY: 74360

Gnomad4 AFR AF: 0.125

Gnomad4 AMR AF: 0.333

Gnomad4 ASJ AF: 0.323

Gnomad4 EAS AF: 0.325

Gnomad4 SAS AF: 0.296

Gnomad4 FIN AF: 0.231

Gnomad4 NFE AF: 0.238

Gnomad4 OTH AF: 0.250

Alfa AF: 0.231 Hom.: 989

Bravo AF: 0.225

Asia WGS AF: 0.307 AC: 1066 AN: 3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	4.8
DANN	Benign	0.67

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: rs1158101; hg19: chr4-74363282;