rs7437940

Variant names:

• chr4-7885773-T-C
• rs7437940
• NM_001134647.2:c.-2-13693A>G

Variant summary

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

The NM_001134647.2(AFAP1):​c.-2-13693A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.428 in 152,128 control chromosomes in the GnomAD database, including 16,609 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 0.43 (16609 hom., cov: 33)
• Consequence: AFAP1 NM_001134647.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.55
• Publications: 14 publications found

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

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.94).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.591 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001134647.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	AFAP1	NM_001134647.2	MANE Select	c.-2-13693A>G		intron	N/A	NP_001128119.1
	AFAP1	NM_001371091.1		c.-3+9292A>G		intron	N/A	NP_001358020.1
	AFAP1	NM_198595.3		c.-2-13693A>G		intron	N/A	NP_940997.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	AFAP1	ENST00000420658.6	TSL:2 MANE Select	c.-2-13693A>G		intron	N/A	ENSP00000410689.1
	AFAP1	ENST00000358461.6	TSL:2	c.-2-13693A>G		intron	N/A	ENSP00000351245.2

Frequencies

GnomAD3 genomes AF: 0.428 AC: 65120 AN: 152010 Hom.: 16604 Cov.: 33

Gnomad AFR AF: 0.182

Gnomad AMI AF: 0.452

Gnomad AMR AF: 0.371

Gnomad ASJ AF: 0.502

Gnomad EAS AF: 0.170

Gnomad SAS AF: 0.289

Gnomad FIN AF: 0.554

Gnomad MID AF: 0.525

Gnomad NFE AF: 0.596

Gnomad OTH AF: 0.458

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

GnomAD4 genome AF: 0.428 AC: 65153 AN: 152128 Hom.: 16609 Cov.: 33 AF XY: 0.421 AC XY: 31284 AN XY: 74354

African (AFR) AF: 0.183 AC: 7597 AN: 41534

American (AMR) AF: 0.370 AC: 5656 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.502 AC: 1742 AN: 3468

East Asian (EAS) AF: 0.170 AC: 878 AN: 5176

South Asian (SAS) AF: 0.290 AC: 1400 AN: 4820

European-Finnish (FIN) AF: 0.554 AC: 5855 AN: 10564

Middle Eastern (MID) AF: 0.534 AC: 157 AN: 294

European-Non Finnish (NFE) AF: 0.596 AC: 40495 AN: 67966

Other (OTH) AF: 0.455 AC: 961 AN: 2110

Alfa AF: 0.539 Hom.: 94773

Bravo AF: 0.407

Asia WGS AF: 0.255 AC: 891 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	0.025
DANN	Benign	0.24
PhyloP100		-1.5
Mutation Taster		=100/0	polymorphism (auto)

Splicing

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

Other links and lift over

dbSNP: rs7437940; hg19: chr4-7887500;