NM_001134647.2:c.-2-28196T>G

Variant names:

• chr4-7900276-A-C
• rs4478172
• NM_001134647.2:c.-2-28196T>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.-2-28196T>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
• Publications: 8 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=-0.91).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.501 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.-2-28196T>G		intron	N/A	NP_001128119.1
	AFAP1	NM_001371091.1		c.-780-4434T>G		intron	N/A	NP_001358020.1
	AFAP1	NM_198595.3		c.-2-28196T>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.-2-28196T>G		intron	N/A	ENSP00000410689.1
	AFAP1	ENST00000358461.6	TSL:2	c.-2-28196T>G		intron	N/A	ENSP00000351245.2

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

African (AFR) AF: 0.457 AC: 17930 AN: 39230

American (AMR) AF: 0.362 AC: 5088 AN: 14074

Ashkenazi Jewish (ASJ) AF: 0.295 AC: 927 AN: 3146

East Asian (EAS) AF: 0.517 AC: 2618 AN: 5062

South Asian (SAS) AF: 0.370 AC: 1654 AN: 4476

European-Finnish (FIN) AF: 0.304 AC: 2790 AN: 9166

Middle Eastern (MID) AF: 0.255 AC: 70 AN: 274

European-Non Finnish (NFE) AF: 0.294 AC: 17536 AN: 59692

Other (OTH) AF: 0.359 AC: 674 AN: 1878

Alfa AF: 0.275 Hom.: 24484

Bravo AF: 0.336

Asia WGS AF: 0.402 AC: 1394 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	1.4
DANN	Benign	0.68
PhyloP100		-0.26
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: rs4478172; hg19: chr4-7902003;