16-56386682-G-A

Variant names:

• chr16-56386682-G-A
• rs2440468
• NM_001144.6:c.1277-660C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001144.6(AMFR):​c.1277-660C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.586 in 152,078 control chromosomes in the GnomAD database, including 27,295 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 0.59 (27295 hom., cov: 33)
• Consequence: AMFR NM_001144.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.786
• Publications: 16 publications found

Genes affected

AMFR (HGNC:463): (autocrine motility factor receptor) This locus encodes a glycosylated transmembrane receptor. Its ligand, autocrine motility factor, is a tumor motility-stimulating protein secreted by tumor cells. The encoded receptor is also a member of the E3 ubiquitin ligase family of proteins. It catalyzes ubiquitination and endoplasmic reticulum-associated degradation of specific proteins. [provided by RefSeq, Feb 2012]

AMFR Gene-Disease associations (from GenCC):

• spastic paraplegia 89, autosomal recessive

  Inheritance: AR Classification: STRONG, MODERATE Submitted by: G2P, Labcorp Genetics (formerly Invitae)

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.93).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.751 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
AMFR	NM_001144.6	c.1277-660C>T		intron_variant	Intron 9 of 13	ENST00000290649.10	NP_001135.3
AMFR	NM_001323512.2	c.1373-660C>T		intron_variant	Intron 10 of 14		NP_001310441.1
AMFR	NM_001323511.2	c.992-660C>T		intron_variant	Intron 9 of 13		NP_001310440.1
AMFR	XM_005255890.5	c.992-660C>T		intron_variant	Intron 9 of 13		XP_005255947.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
AMFR	ENST00000290649.10	c.1277-660C>T		intron_variant	Intron 9 of 13	1	NM_001144.6	ENSP00000290649.5
AMFR	ENST00000492830.5	c.245-660C>T		intron_variant	Intron 2 of 6	2		ENSP00000473636.1
AMFR	ENST00000567738.1	c.518-660C>T		intron_variant	Intron 4 of 7	5		ENSP00000456288.1
AMFR	ENST00000568762.1	n.44-660C>T		intron_variant	Intron 1 of 1	3

Frequencies

GnomAD3 genomes AF: 0.586 AC: 89020 AN: 151960 Hom.: 27269 Cov.: 33

Gnomad AFR AF: 0.759

Gnomad AMI AF: 0.579

Gnomad AMR AF: 0.548

Gnomad ASJ AF: 0.531

Gnomad EAS AF: 0.438

Gnomad SAS AF: 0.605

Gnomad FIN AF: 0.392

Gnomad MID AF: 0.475

Gnomad NFE AF: 0.533

Gnomad OTH AF: 0.564

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

GnomAD4 genome AF: 0.586 AC: 89086 AN: 152078 Hom.: 27295 Cov.: 33 AF XY: 0.579 AC XY: 43040 AN XY: 74312

African (AFR) AF: 0.758 AC: 31468 AN: 41498

American (AMR) AF: 0.548 AC: 8365 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.531 AC: 1842 AN: 3468

East Asian (EAS) AF: 0.437 AC: 2262 AN: 5174

South Asian (SAS) AF: 0.605 AC: 2920 AN: 4824

European-Finnish (FIN) AF: 0.392 AC: 4142 AN: 10554

Middle Eastern (MID) AF: 0.476 AC: 140 AN: 294

European-Non Finnish (NFE) AF: 0.533 AC: 36239 AN: 67966

Other (OTH) AF: 0.559 AC: 1181 AN: 2114

Alfa AF: 0.531 Hom.: 9932

Bravo AF: 0.604

Asia WGS AF: 0.546 AC: 1899 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	0.084
DANN	Benign	0.39
PhyloP100		-0.79
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: rs2440468; hg19: chr16-56420594;