rs721041

Positions:

• chr10-114375585-A-G

Variant summary

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

The NM_001001936.3(AFAP1L2):​c.16+28855T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.553 in 152,052 control chromosomes in the GnomAD database, including 24,448 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 0.55 (24448 hom., cov: 33)
• Consequence: AFAP1L2 NM_001001936.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.95

Genes affected

AFAP1L2 (HGNC:25901): (actin filament associated protein 1 like 2) Enables SH2 domain binding activity; SH3 domain binding activity; and protein tyrosine kinase activator activity. Involved in several processes, including positive regulation of epidermal growth factor receptor signaling pathway; regulation of gene expression; and regulation of mitotic cell cycle. Located in cytosol and plasma membrane. [provided by Alliance of Genome Resources, Apr 2022]

AFAP1L2 (HGNC:):

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 = 0.659 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
AFAP1L2	NM_001001936.3	c.16+28855T>C		intron_variant		ENST00000304129.9	NP_001001936.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
AFAP1L2	ENST00000304129.9	c.16+28855T>C		intron_variant		1	NM_001001936.3	ENSP00000303042.4

Frequencies

GnomAD3 genomes AF: 0.553 AC: 84092 AN: 151934 Hom.: 24434 Cov.: 33

Gnomad AFR AF: 0.359

Gnomad AMI AF: 0.541

Gnomad AMR AF: 0.591

Gnomad ASJ AF: 0.611

Gnomad EAS AF: 0.679

Gnomad SAS AF: 0.548

Gnomad FIN AF: 0.711

Gnomad MID AF: 0.592

Gnomad NFE AF: 0.625

Gnomad OTH AF: 0.586

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

GnomAD4 genome AF: 0.553 AC: 84132 AN: 152052 Hom.: 24448 Cov.: 33 AF XY: 0.557 AC XY: 41434 AN XY: 74330

Gnomad4 AFR AF: 0.359

Gnomad4 AMR AF: 0.591

Gnomad4 ASJ AF: 0.611

Gnomad4 EAS AF: 0.678

Gnomad4 SAS AF: 0.550

Gnomad4 FIN AF: 0.711

Gnomad4 NFE AF: 0.625

Gnomad4 OTH AF: 0.588

Alfa AF: 0.582 Hom.: 3320

Bravo AF: 0.543

Asia WGS AF: 0.591 AC: 2057 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	0.099
DANN	Benign	0.41

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

Publications

LitVar

Other links and lift over

dbSNP: rs721041; hg19: chr10-116135344;