chr4-7929955-A-C

Variant names:

• chr4-7929955-A-C
• rs11930623
• NM_001134647.2:c.-3+9701T>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.-3+9701T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.293 in 152,096 control chromosomes in the GnomAD database, including 7,882 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 0.29 (7882 hom., cov: 33)
• Consequence: AFAP1 NM_001134647.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.00600
• Publications: 16 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=-0.88).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.404 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.-3+9701T>G		intron	N/A	NP_001128119.1
	AFAP1	NM_001371091.1		c.-781+9701T>G		intron	N/A	NP_001358020.1
	AFAP1	NM_198595.3		c.-3+9701T>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.-3+9701T>G		intron	N/A	ENSP00000410689.1
	AFAP1	ENST00000358461.6	TSL:2	c.-3+9701T>G		intron	N/A	ENSP00000351245.2

Frequencies

GnomAD3 genomes AF: 0.293 AC: 44492 AN: 151978 Hom.: 7886 Cov.: 33

Gnomad AFR AF: 0.124

Gnomad AMI AF: 0.338

Gnomad AMR AF: 0.265

Gnomad ASJ AF: 0.412

Gnomad EAS AF: 0.0395

Gnomad SAS AF: 0.170

Gnomad FIN AF: 0.382

Gnomad MID AF: 0.386

Gnomad NFE AF: 0.408

Gnomad OTH AF: 0.323

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

GnomAD4 genome AF: 0.293 AC: 44511 AN: 152096 Hom.: 7882 Cov.: 33 AF XY: 0.285 AC XY: 21213 AN XY: 74334

African (AFR) AF: 0.124 AC: 5161 AN: 41518

American (AMR) AF: 0.264 AC: 4036 AN: 15264

Ashkenazi Jewish (ASJ) AF: 0.412 AC: 1428 AN: 3470

East Asian (EAS) AF: 0.0394 AC: 204 AN: 5180

South Asian (SAS) AF: 0.171 AC: 827 AN: 4826

European-Finnish (FIN) AF: 0.382 AC: 4029 AN: 10558

Middle Eastern (MID) AF: 0.381 AC: 112 AN: 294

European-Non Finnish (NFE) AF: 0.408 AC: 27724 AN: 67960

Other (OTH) AF: 0.322 AC: 682 AN: 2116

Alfa AF: 0.344 Hom.: 8827

Bravo AF: 0.280

Asia WGS AF: 0.128 AC: 448 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	5.1
DANN	Benign	0.74
PhyloP100		0.0060
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: rs11930623; hg19: chr4-7931682;