6-167901335-A-G

Position:

• chr6-167901335-A-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001386888.1(AFDN):​c.1581-982A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.345 in 151,900 control chromosomes in the GnomAD database, including 9,772 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 0.34 (9772 hom., cov: 31)
• Consequence: AFDN NM_001386888.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.39

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

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.01).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.58 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
AFDN	NM_001386888.1	c.1581-982A>G		intron_variant		ENST00000683244.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
AFDN	ENST00000683244.1	c.1581-982A>G		intron_variant			NM_001386888.1	P4

Frequencies

GnomAD3 genomes AF: 0.344 AC: 52278 AN: 151784 Hom.: 9753 Cov.: 31

Gnomad AFR AF: 0.226

Gnomad AMI AF: 0.487

Gnomad AMR AF: 0.361

Gnomad ASJ AF: 0.352

Gnomad EAS AF: 0.597

Gnomad SAS AF: 0.428

Gnomad FIN AF: 0.401

Gnomad MID AF: 0.326

Gnomad NFE AF: 0.376

Gnomad OTH AF: 0.357

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

GnomAD4 genome AF: 0.345 AC: 52334 AN: 151900 Hom.: 9772 Cov.: 31 AF XY: 0.353 AC XY: 26205 AN XY: 74242

Gnomad4 AFR AF: 0.227

Gnomad4 AMR AF: 0.362

Gnomad4 ASJ AF: 0.352

Gnomad4 EAS AF: 0.598

Gnomad4 SAS AF: 0.430

Gnomad4 FIN AF: 0.401

Gnomad4 NFE AF: 0.376

Gnomad4 OTH AF: 0.359

Alfa AF: 0.369 Hom.: 4974

Bravo AF: 0.334

Asia WGS AF: 0.502 AC: 1744 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.41
DANN	Benign	0.35

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.050		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs3800524; hg19: chr6-168302015;