rs2440468

Variant names:

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

Your query was ambiguous. Multiple possible variants found:

• chr16-56386682-G-A
• chr16-56386682-G-C

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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001144.6. 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
	AMFR	NM_001144.6	MANE Select	c.1277-660C>T		intron	N/A	NP_001135.3
	AMFR	NM_001323512.2		c.1373-660C>T		intron	N/A	NP_001310441.1
	AMFR	NM_001323511.2		c.992-660C>T		intron	N/A	NP_001310440.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	AMFR	ENST00000290649.10	TSL:1 MANE Select	c.1277-660C>T		intron	N/A	ENSP00000290649.5
	AMFR	ENST00000861442.1		c.1277-660C>T		intron	N/A	ENSP00000531501.1
	AMFR	ENST00000861443.1		c.1277-660C>T		intron	N/A	ENSP00000531502.1

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 v4.9

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;