rs4383619

Positions:

• chr4-7861781-T-C

Variant summary

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

The NM_001134647.2(AFAP1):​c.226-6207A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.789 in 152,258 control chromosomes in the GnomAD database, including 47,672 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 0.79 (47672 hom., cov: 34)
• Consequence: AFAP1 NM_001134647.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.390

Genes affected

AFAP1 (HGNC:24017): (actin filament associated protein 1) The protein encoded by this gene is a Src binding partner. It may represent a potential modulator of actin filament integrity in response to cellular signals, and may function as an adaptor protein by linking Src family members and/or other signaling proteins to actin filaments. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Aug 2008]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.948 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
AFAP1	NM_001134647.2	c.226-6207A>G		intron_variant		ENST00000420658.6	NP_001128119.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
AFAP1	ENST00000420658.6	c.226-6207A>G		intron_variant		2	NM_001134647.2	ENSP00000410689

Frequencies

GnomAD3 genomes AF: 0.789 AC: 120032 AN: 152140 Hom.: 47623 Cov.: 34

Gnomad AFR AF: 0.732

Gnomad AMI AF: 0.704

Gnomad AMR AF: 0.753

Gnomad ASJ AF: 0.776

Gnomad EAS AF: 0.970

Gnomad SAS AF: 0.775

Gnomad FIN AF: 0.833

Gnomad MID AF: 0.753

Gnomad NFE AF: 0.814

Gnomad OTH AF: 0.781

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

GnomAD4 genome AF: 0.789 AC: 120131 AN: 152258 Hom.: 47672 Cov.: 34 AF XY: 0.789 AC XY: 58745 AN XY: 74454

Gnomad4 AFR AF: 0.732

Gnomad4 AMR AF: 0.753

Gnomad4 ASJ AF: 0.776

Gnomad4 EAS AF: 0.970

Gnomad4 SAS AF: 0.774

Gnomad4 FIN AF: 0.833

Gnomad4 NFE AF: 0.814

Gnomad4 OTH AF: 0.782

Alfa AF: 0.802 Hom.: 22449

Bravo AF: 0.780

Asia WGS AF: 0.858 AC: 2984 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	3.0
DANN	Benign	0.52

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: rs4383619; hg19: chr4-7863508;