NM_001001936.3:c.16+28855T>C

Variant names:

• chr10-114375585-A-G
• rs721041
• NM_001001936.3:c.16+28855T>C

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 0 publications found

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

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 = 0.659 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
AFAP1L2	NM_001001936.3	c.16+28855T>C		intron_variant	Intron 1 of 18	ENST00000304129.9	NP_001001936.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
AFAP1L2	ENST00000304129.9	c.16+28855T>C		intron_variant	Intron 1 of 18	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

African (AFR) AF: 0.359 AC: 14891 AN: 41444

American (AMR) AF: 0.591 AC: 9031 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.611 AC: 2119 AN: 3470

East Asian (EAS) AF: 0.678 AC: 3511 AN: 5178

South Asian (SAS) AF: 0.550 AC: 2644 AN: 4810

European-Finnish (FIN) AF: 0.711 AC: 7518 AN: 10576

Middle Eastern (MID) AF: 0.602 AC: 177 AN: 294

European-Non Finnish (NFE) AF: 0.625 AC: 42508 AN: 67968

Other (OTH) AF: 0.588 AC: 1240 AN: 2108

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
PhyloP100		-1.9
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs721041; hg19: chr10-116135344;