rs2300081

Variant names:

• chr6-167878290-A-G
• rs2300081
• NM_001386888.1:c.740-2070A>G

Variant summary

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

The NM_001386888.1(AFDN):​c.740-2070A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.077 in 152,128 control chromosomes in the GnomAD database, including 568 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 0.077 (568 hom., cov: 32)
• Consequence: AFDN NM_001386888.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.489
• Publications: 1 publications found

Genes affected

AFDN (HGNC:7137): (afadin, adherens junction formation factor) This gene encodes a multi-domain protein involved in signaling and organization of cell junctions during embryogenesis. It has also been identified as the fusion partner of acute lymphoblastic leukemia (ALL-1) gene, involved in acute myeloid leukemias with t(6;11)(q27;q23) translocation. Alternatively spliced transcript variants encoding different isoforms have been described for this gene, however, not all have been fully characterized.[provided by RefSeq, May 2011]

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.145 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
AFDN	NM_001386888.1	c.740-2070A>G		intron_variant	Intron 5 of 33	ENST00000683244.1	NP_001373817.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
AFDN	ENST00000683244.1	c.740-2070A>G		intron_variant	Intron 5 of 33		NM_001386888.1	ENSP00000507324.1

Frequencies

GnomAD3 genomes AF: 0.0771 AC: 11716 AN: 152010 Hom.: 567 Cov.: 32

Gnomad AFR AF: 0.0320

Gnomad AMI AF: 0.0987

Gnomad AMR AF: 0.150

Gnomad ASJ AF: 0.0510

Gnomad EAS AF: 0.114

Gnomad SAS AF: 0.0710

Gnomad FIN AF: 0.0616

Gnomad MID AF: 0.0854

Gnomad NFE AF: 0.0889

Gnomad OTH AF: 0.0851

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

GnomAD4 genome AF: 0.0770 AC: 11719 AN: 152128 Hom.: 568 Cov.: 32 AF XY: 0.0771 AC XY: 5737 AN XY: 74362

African (AFR) AF: 0.0319 AC: 1324 AN: 41508

American (AMR) AF: 0.150 AC: 2292 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.0510 AC: 177 AN: 3472

East Asian (EAS) AF: 0.114 AC: 586 AN: 5158

South Asian (SAS) AF: 0.0709 AC: 342 AN: 4824

European-Finnish (FIN) AF: 0.0616 AC: 652 AN: 10584

Middle Eastern (MID) AF: 0.0918 AC: 27 AN: 294

European-Non Finnish (NFE) AF: 0.0889 AC: 6046 AN: 67990

Other (OTH) AF: 0.0866 AC: 183 AN: 2114

Alfa AF: 0.0845 Hom.: 78

Bravo AF: 0.0809

Asia WGS AF: 0.0890 AC: 310 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	1.4
DANN	Benign	0.58
PhyloP100		-0.49
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: rs2300081; hg19: chr6-168278970;