16-56383135-T-C

Variant names:

• chr16-56383135-T-C
• rs2440467
• NM_001144.6:c.1380+2784A>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.1380+2784A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.662 in 152,084 control chromosomes in the GnomAD database, including 35,264 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 0.66 (35264 hom., cov: 31)
• Consequence: AMFR NM_001144.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -3.37
• Publications: 17 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: Labcorp Genetics (formerly Invitae), G2P

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.892 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.1380+2784A>G		intron	N/A	NP_001135.3
	AMFR	NM_001323512.2		c.1476+2784A>G		intron	N/A	NP_001310441.1
	AMFR	NM_001323511.2		c.1095+2784A>G		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.1380+2784A>G		intron	N/A	ENSP00000290649.5	Q9UKV5
	AMFR	ENST00000861442.1		c.1380+2784A>G		intron	N/A	ENSP00000531501.1
	AMFR	ENST00000861443.1		c.1380+2784A>G		intron	N/A	ENSP00000531502.1

Frequencies

GnomAD3 genomes AF: 0.662 AC: 100566 AN: 151966 Hom.: 35213 Cov.: 31

Gnomad AFR AF: 0.900

Gnomad AMI AF: 0.588

Gnomad AMR AF: 0.598

Gnomad ASJ AF: 0.550

Gnomad EAS AF: 0.597

Gnomad SAS AF: 0.725

Gnomad FIN AF: 0.442

Gnomad MID AF: 0.506

Gnomad NFE AF: 0.574

Gnomad OTH AF: 0.631

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

GnomAD4 genome AF: 0.662 AC: 100667 AN: 152084 Hom.: 35264 Cov.: 31 AF XY: 0.656 AC XY: 48738 AN XY: 74318

African (AFR) AF: 0.900 AC: 37359 AN: 41506

American (AMR) AF: 0.598 AC: 9145 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.550 AC: 1906 AN: 3466

East Asian (EAS) AF: 0.597 AC: 3076 AN: 5156

South Asian (SAS) AF: 0.725 AC: 3493 AN: 4820

European-Finnish (FIN) AF: 0.442 AC: 4668 AN: 10564

Middle Eastern (MID) AF: 0.507 AC: 148 AN: 292

European-Non Finnish (NFE) AF: 0.574 AC: 39008 AN: 67972

Other (OTH) AF: 0.629 AC: 1328 AN: 2110

Alfa AF: 0.589 Hom.: 4003

Bravo AF: 0.683

Asia WGS AF: 0.710 AC: 2469 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.17
DANN	Benign	0.69
PhyloP100		-3.4
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: rs2440467; hg19: chr16-56417047; COSMIC: COSV51924626; COSMIC: COSV51924626;