rs4619890

Positions:

• chr4-7851433-G-A

Variant summary

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

The NM_001134647.2(AFAP1):​c.334+4033C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.404 in 152,054 control chromosomes in the GnomAD database, including 14,071 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 0.40 (14071 hom., cov: 32)
• Consequence: AFAP1 NM_001134647.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.264

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=-0.95).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.508 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
AFAP1	NM_001134647.2	c.334+4033C>T		intron_variant		ENST00000420658.6	NP_001128119.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
AFAP1	ENST00000420658.6	c.334+4033C>T		intron_variant		2	NM_001134647.2	ENSP00000410689

Frequencies

GnomAD3 genomes AF: 0.405 AC: 61475 AN: 151936 Hom.: 14073 Cov.: 32

Gnomad AFR AF: 0.183

Gnomad AMI AF: 0.477

Gnomad AMR AF: 0.431

Gnomad ASJ AF: 0.539

Gnomad EAS AF: 0.294

Gnomad SAS AF: 0.384

Gnomad FIN AF: 0.543

Gnomad MID AF: 0.506

Gnomad NFE AF: 0.513

Gnomad OTH AF: 0.434

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

GnomAD4 genome AF: 0.404 AC: 61474 AN: 152054 Hom.: 14071 Cov.: 32 AF XY: 0.404 AC XY: 30060 AN XY: 74334

Gnomad4 AFR AF: 0.182

Gnomad4 AMR AF: 0.431

Gnomad4 ASJ AF: 0.539

Gnomad4 EAS AF: 0.294

Gnomad4 SAS AF: 0.385

Gnomad4 FIN AF: 0.543

Gnomad4 NFE AF: 0.513

Gnomad4 OTH AF: 0.434

Alfa AF: 0.494 Hom.: 38235

Bravo AF: 0.387

Asia WGS AF: 0.327 AC: 1139 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	3.4
DANN	Benign	0.23

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: rs4619890; hg19: chr4-7853160;