chr4-7845937-G-A

Variant names:

• chr4-7845937-G-A
• rs28495790
• NM_001134647.2:c.335-2587C>T

Variant summary

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

The NM_001134647.2(AFAP1):​c.335-2587C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.4 in 151,988 control chromosomes in the GnomAD database, including 13,834 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 (13834 hom., cov: 32)
• Consequence: AFAP1 NM_001134647.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.188
• Publications: 5 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=-0.87).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.505 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	AFAP1	NM_001134647.2	MANE Select	c.335-2587C>T		intron	N/A	NP_001128119.1
	AFAP1	NM_001371090.1		c.335-2587C>T		intron	N/A	NP_001358019.1
	AFAP1	NM_001371091.1		c.335-2587C>T		intron	N/A	NP_001358020.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	AFAP1	ENST00000420658.6	TSL:2 MANE Select	c.335-2587C>T		intron	N/A	ENSP00000410689.1
	AFAP1	ENST00000360265.9	TSL:1	c.335-2587C>T		intron	N/A	ENSP00000353402.4
	AFAP1	ENST00000382543.4	TSL:5	c.335-2587C>T		intron	N/A	ENSP00000371983.3

Frequencies

GnomAD3 genomes AF: 0.400 AC: 60818 AN: 151868 Hom.: 13836 Cov.: 32

Gnomad AFR AF: 0.180

Gnomad AMI AF: 0.478

Gnomad AMR AF: 0.425

Gnomad ASJ AF: 0.527

Gnomad EAS AF: 0.281

Gnomad SAS AF: 0.366

Gnomad FIN AF: 0.542

Gnomad MID AF: 0.519

Gnomad NFE AF: 0.509

Gnomad OTH AF: 0.432

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

GnomAD4 genome AF: 0.400 AC: 60817 AN: 151988 Hom.: 13834 Cov.: 32 AF XY: 0.400 AC XY: 29732 AN XY: 74268

African (AFR) AF: 0.180 AC: 7464 AN: 41462

American (AMR) AF: 0.424 AC: 6474 AN: 15262

Ashkenazi Jewish (ASJ) AF: 0.527 AC: 1826 AN: 3468

East Asian (EAS) AF: 0.280 AC: 1443 AN: 5148

South Asian (SAS) AF: 0.368 AC: 1775 AN: 4822

European-Finnish (FIN) AF: 0.542 AC: 5717 AN: 10546

Middle Eastern (MID) AF: 0.514 AC: 151 AN: 294

European-Non Finnish (NFE) AF: 0.509 AC: 34620 AN: 67964

Other (OTH) AF: 0.432 AC: 911 AN: 2110

Alfa AF: 0.492 Hom.: 8125

Bravo AF: 0.382

Asia WGS AF: 0.318 AC: 1107 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	0.46
DANN	Benign	0.89
PhyloP100		-0.19
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs28495790; hg19: chr4-7847664;