NM_152406.4:c.16+6363C>A

Variant names:

• chr5-149278347-C-A
• rs1438693
• NM_152406.4:c.16+6363C>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_152406.4(AFAP1L1):​c.16+6363C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.529 in 151,858 control chromosomes in the GnomAD database, including 21,726 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 0.53 (21726 hom., cov: 31)
• Consequence: AFAP1L1 NM_152406.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.184
• Publications: 3 publications found

Genes affected

AFAP1L1 (HGNC:26714): (actin filament associated protein 1 like 1) Predicted to enable SH3 domain binding activity. Predicted to be located in cell junction; cell projection; and podosome. Predicted to be active in cytosol. [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=-0.88).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.754 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
AFAP1L1	NM_152406.4	c.16+6363C>A		intron_variant	Intron 1 of 18	ENST00000296721.9	NP_689619.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
AFAP1L1	ENST00000296721.9	c.16+6363C>A		intron_variant	Intron 1 of 18	1	NM_152406.4	ENSP00000296721.4
AFAP1L1	ENST00000515000.1	c.16+6363C>A		intron_variant	Intron 1 of 17	1		ENSP00000424427.1
AFAP1L1	ENST00000455574.6	n.114+6363C>A		intron_variant	Intron 1 of 8	1
AFAP1L1	ENST00000522492.1	n.90+6363C>A		intron_variant	Intron 1 of 7	3

Frequencies

GnomAD3 genomes AF: 0.529 AC: 80208 AN: 151738 Hom.: 21694 Cov.: 31

Gnomad AFR AF: 0.441

Gnomad AMI AF: 0.471

Gnomad AMR AF: 0.616

Gnomad ASJ AF: 0.539

Gnomad EAS AF: 0.774

Gnomad SAS AF: 0.589

Gnomad FIN AF: 0.515

Gnomad MID AF: 0.576

Gnomad NFE AF: 0.541

Gnomad OTH AF: 0.535

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

GnomAD4 genome AF: 0.529 AC: 80280 AN: 151858 Hom.: 21726 Cov.: 31 AF XY: 0.530 AC XY: 39339 AN XY: 74200

African (AFR) AF: 0.441 AC: 18256 AN: 41402

American (AMR) AF: 0.617 AC: 9422 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.539 AC: 1869 AN: 3466

East Asian (EAS) AF: 0.774 AC: 3982 AN: 5146

South Asian (SAS) AF: 0.591 AC: 2826 AN: 4784

European-Finnish (FIN) AF: 0.515 AC: 5422 AN: 10530

Middle Eastern (MID) AF: 0.568 AC: 167 AN: 294

European-Non Finnish (NFE) AF: 0.541 AC: 36771 AN: 67928

Other (OTH) AF: 0.537 AC: 1135 AN: 2114

Alfa AF: 0.538 Hom.: 60010

Bravo AF: 0.535

Asia WGS AF: 0.667 AC: 2321 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	2.1
DANN	Benign	0.83
PhyloP100		-0.18
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: rs1438693; hg19: chr5-148657910;