rs646668

Positions:

• chr10-114378275-G-A

Variant summary

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

The NM_001001936.3(AFAP1L2):​c.16+26165C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.483 in 152,080 control chromosomes in the GnomAD database, including 18,348 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 0.48 (18348 hom., cov: 33)
• Consequence: AFAP1L2 NM_001001936.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.915

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.94).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.61 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
AFAP1L2	NM_001001936.3	c.16+26165C>T		intron_variant		ENST00000304129.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
AFAP1L2	ENST00000304129.9	c.16+26165C>T		intron_variant		1	NM_001001936.3	P4

Frequencies

GnomAD3 genomes AF: 0.482 AC: 73314 AN: 151962 Hom.: 18315 Cov.: 33

Gnomad AFR AF: 0.616

Gnomad AMI AF: 0.505

Gnomad AMR AF: 0.447

Gnomad ASJ AF: 0.458

Gnomad EAS AF: 0.323

Gnomad SAS AF: 0.500

Gnomad FIN AF: 0.329

Gnomad MID AF: 0.478

Gnomad NFE AF: 0.445

Gnomad OTH AF: 0.470

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

GnomAD4 genome AF: 0.483 AC: 73400 AN: 152080 Hom.: 18348 Cov.: 33 AF XY: 0.478 AC XY: 35524 AN XY: 74346

Gnomad4 AFR AF: 0.617

Gnomad4 AMR AF: 0.447

Gnomad4 ASJ AF: 0.458

Gnomad4 EAS AF: 0.324

Gnomad4 SAS AF: 0.500

Gnomad4 FIN AF: 0.329

Gnomad4 NFE AF: 0.445

Gnomad4 OTH AF: 0.467

Alfa AF: 0.472 Hom.: 2152

Bravo AF: 0.490

Asia WGS AF: 0.442 AC: 1534 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	0.11
DANN	Benign	0.60

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: rs646668; hg19: chr10-116138034;