chr6-167901335-A-G

Variant names:

• chr6-167901335-A-G
• rs3800524
• NM_001386888.1:c.1581-982A>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.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
• Publications: 2 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=-1.01).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.58 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001386888.1. 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
	AFDN	NM_001386888.1	MANE Select	c.1581-982A>G		intron	N/A	NP_001373817.1
	AFDN	NM_001366320.2		c.1581-982A>G		intron	N/A	NP_001353249.1
	AFDN	NM_001366319.2		c.1581-982A>G		intron	N/A	NP_001353248.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	AFDN	ENST00000683244.1	MANE Select	c.1581-982A>G		intron	N/A	ENSP00000507324.1
	AFDN	ENST00000366806.6	TSL:1	c.1458-982A>G		intron	N/A	ENSP00000355771.3
	AFDN	ENST00000392108.7	TSL:1	c.1581-982A>G		intron	N/A	ENSP00000375956.3

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

African (AFR) AF: 0.227 AC: 9391 AN: 41446

American (AMR) AF: 0.362 AC: 5522 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.352 AC: 1222 AN: 3470

East Asian (EAS) AF: 0.598 AC: 3084 AN: 5160

South Asian (SAS) AF: 0.430 AC: 2064 AN: 4798

European-Finnish (FIN) AF: 0.401 AC: 4221 AN: 10526

Middle Eastern (MID) AF: 0.327 AC: 96 AN: 294

European-Non Finnish (NFE) AF: 0.376 AC: 25533 AN: 67918

Other (OTH) AF: 0.359 AC: 757 AN: 2106

Alfa AF: 0.366 Hom.: 5434

Bravo AF: 0.334

Asia WGS AF: 0.502 AC: 1744 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.41
DANN	Benign	0.35
PhyloP100		-1.4
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs3800524; hg19: chr6-168302015;