rs4751674

Positions:

• chr10-114379270-T-C
• chr10-114379270-T-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+25170A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.704 in 151,172 control chromosomes in the GnomAD database, including 37,985 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 0.70 (37985 hom., cov: 27)
• Consequence: AFAP1L2 NM_001001936.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.333

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=-0.9).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.79 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
AFAP1L2	NM_001001936.3	c.16+25170A>G		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+25170A>G		intron_variant		1	NM_001001936.3	ENSP00000303042	P4

Frequencies

GnomAD3 genomes AF: 0.704 AC: 106415 AN: 151068 Hom.: 37964 Cov.: 27

Gnomad AFR AF: 0.590

Gnomad AMI AF: 0.551

Gnomad AMR AF: 0.792

Gnomad ASJ AF: 0.804

Gnomad EAS AF: 0.811

Gnomad SAS AF: 0.807

Gnomad FIN AF: 0.770

Gnomad MID AF: 0.763

Gnomad NFE AF: 0.724

Gnomad OTH AF: 0.739

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

GnomAD4 genome AF: 0.704 AC: 106472 AN: 151172 Hom.: 37985 Cov.: 27 AF XY: 0.710 AC XY: 52391 AN XY: 73800

Gnomad4 AFR AF: 0.590

Gnomad4 AMR AF: 0.792

Gnomad4 ASJ AF: 0.804

Gnomad4 EAS AF: 0.810

Gnomad4 SAS AF: 0.808

Gnomad4 FIN AF: 0.770

Gnomad4 NFE AF: 0.724

Gnomad4 OTH AF: 0.738

Alfa AF: 0.730 Hom.: 93093

Bravo AF: 0.701

Asia WGS AF: 0.737 AC: 2564 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	9.1
DANN	Benign	0.81

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: rs4751674; hg19: chr10-116139029;