rs6838291

Positions:

• chr4-7916079-C-G
• chr4-7916079-C-T

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001134647.2(AFAP1):​c.-3+23577G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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: not found (cov: 31)
• Consequence: AFAP1 NM_001134647.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.338

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 Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
AFAP1	NM_001134647.2	c.-3+23577G>C		intron_variant		ENST00000420658.6	NP_001128119.1
AFAP1	NM_001371091.1	c.-780-20237G>C		intron_variant			NP_001358020.1
AFAP1	NM_198595.3	c.-3+23577G>C		intron_variant			NP_940997.1
AFAP1	XM_006713909.4	c.61+22513G>C		intron_variant			XP_006713972.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
AFAP1	ENST00000420658.6	c.-3+23577G>C		intron_variant		2	NM_001134647.2	ENSP00000410689
AFAP1	ENST00000358461.6	c.-3+23577G>C		intron_variant		2		ENSP00000351245	P1

Frequencies

GnomAD3 genomes Cov.: 31

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

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	1.2
DANN	Benign	0.26

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs6838291; hg19: chr4-7917806;