chr16-56420069-T-C

Variant names:

• chr16-56420069-T-C
• rs6499837
• NM_001144.6:c.255+5004A>G

Variant summary

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

The NM_001144.6(AMFR):​c.255+5004A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.667 in 152,134 control chromosomes in the GnomAD database, including 35,957 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 0.67 (35957 hom., cov: 31)
• Consequence: AMFR NM_001144.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -3.24
• 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=-0.98).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.91 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	AMFR	NM_001144.6	MANE Select	c.255+5004A>G		intron	N/A	NP_001135.3
	AMFR	NM_001323512.2		c.255+5004A>G		intron	N/A	NP_001310441.1
	AMFR	NM_001323511.2		c.-31+4842A>G		intron	N/A	NP_001310440.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	AMFR	ENST00000290649.10	TSL:1 MANE Select	c.255+5004A>G		intron	N/A	ENSP00000290649.5
	AMFR	ENST00000565445.5	TSL:5	c.-31+4842A>G		intron	N/A	ENSP00000456745.1
	AMFR	ENST00000563664.1	TSL:4	c.-31+4762A>G		intron	N/A	ENSP00000455842.1

Frequencies

GnomAD3 genomes AF: 0.667 AC: 101343 AN: 152014 Hom.: 35896 Cov.: 31

Gnomad AFR AF: 0.917

Gnomad AMI AF: 0.587

Gnomad AMR AF: 0.600

Gnomad ASJ AF: 0.549

Gnomad EAS AF: 0.597

Gnomad SAS AF: 0.727

Gnomad FIN AF: 0.441

Gnomad MID AF: 0.510

Gnomad NFE AF: 0.574

Gnomad OTH AF: 0.634

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

GnomAD4 genome AF: 0.667 AC: 101454 AN: 152134 Hom.: 35957 Cov.: 31 AF XY: 0.661 AC XY: 49127 AN XY: 74352

African (AFR) AF: 0.917 AC: 38109 AN: 41540

American (AMR) AF: 0.600 AC: 9157 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.549 AC: 1902 AN: 3466

East Asian (EAS) AF: 0.596 AC: 3080 AN: 5168

South Asian (SAS) AF: 0.726 AC: 3504 AN: 4824

European-Finnish (FIN) AF: 0.441 AC: 4659 AN: 10558

Middle Eastern (MID) AF: 0.510 AC: 149 AN: 292

European-Non Finnish (NFE) AF: 0.574 AC: 39024 AN: 67990

Other (OTH) AF: 0.633 AC: 1336 AN: 2112

Alfa AF: 0.639 Hom.: 6186

Bravo AF: 0.688

Asia WGS AF: 0.711 AC: 2473 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
CADD	Benign	0.050
DANN	Benign	0.67
PhyloP100		-3.2
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs6499837; hg19: chr16-56453981;