rs4478172

chr4-7900276-A-Cchr4-7900276-A-T

Variant summary

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

The NM_001134647.2(AFAP1):c.-2-28196T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.359 in 137,782 control chromosomes in the GnomAD database, including 8,691 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 0.36 (8691 hom., cov: 32)
• Consequence: AFAP1 NM_001134647.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.257

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=-0.91).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.501 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
AFAP1	NM_001134647.2	c.-2-28196T>G		intron_variant		ENST00000420658.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
AFAP1	ENST00000420658.6	c.-2-28196T>G		intron_variant		2	NM_001134647.2
AFAP1	ENST00000358461.6	c.-2-28196T>G		intron_variant		2		P1

Frequencies

GnomAD3 genomes AF: 0.359 AC: 49410 AN: 137666 Hom.: 8678 Cov.: 32

Gnomad AFR AF: 0.457

Gnomad AMI AF: 0.207

Gnomad AMR AF: 0.361

Gnomad ASJ AF: 0.295

Gnomad EAS AF: 0.517

Gnomad SAS AF: 0.371

Gnomad FIN AF: 0.304

Gnomad MID AF: 0.265

Gnomad NFE AF: 0.294

Gnomad OTH AF: 0.360

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

GnomAD4 genome AF: 0.359 AC: 49449 AN: 137782 Hom.: 8691 Cov.: 32 AF XY: 0.361 AC XY: 24250 AN XY: 67140

Gnomad4 AFR AF: 0.457

Gnomad4 AMR AF: 0.362

Gnomad4 ASJ AF: 0.295

Gnomad4 EAS AF: 0.517

Gnomad4 SAS AF: 0.370

Gnomad4 FIN AF: 0.304

Gnomad4 NFE AF: 0.294

Gnomad4 OTH AF: 0.359

Alfa AF: 0.260 Hom.: 10682

Bravo AF: 0.336

Asia WGS AF: 0.402 AC: 1394 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
Cadd	Benign	1.4
Dann	Benign	0.68

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs4478172; hg19: chr4-7902003;