NM_001134647.2:c.-3+23577G>A

Variant names:

• chr4-7916079-C-T
• rs6838291
• NM_001134647.2:c.-3+23577G>A

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+23577G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.195 in 152,006 control chromosomes in the GnomAD database, including 3,139 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 0.20 (3139 hom., cov: 31)
• Consequence: AFAP1 NM_001134647.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.338
• 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=-0.86).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.252 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
AFAP1	NM_001134647.2	c.-3+23577G>A		intron_variant	Intron 1 of 17	ENST00000420658.6	NP_001128119.1
AFAP1	NM_001371091.1	c.-780-20237G>A		intron_variant	Intron 1 of 17		NP_001358020.1
AFAP1	NM_198595.3	c.-3+23577G>A		intron_variant	Intron 1 of 16		NP_940997.1
AFAP1	XM_006713909.4	c.61+22513G>A		intron_variant	Intron 1 of 16		XP_006713972.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
AFAP1	ENST00000420658.6	c.-3+23577G>A		intron_variant	Intron 1 of 17	2	NM_001134647.2	ENSP00000410689.1
AFAP1	ENST00000358461.6	c.-3+23577G>A		intron_variant	Intron 1 of 16	2		ENSP00000351245.2

Frequencies

GnomAD3 genomes AF: 0.195 AC: 29652 AN: 151888 Hom.: 3133 Cov.: 31

Gnomad AFR AF: 0.257

Gnomad AMI AF: 0.156

Gnomad AMR AF: 0.230

Gnomad ASJ AF: 0.185

Gnomad EAS AF: 0.0622

Gnomad SAS AF: 0.218

Gnomad FIN AF: 0.148

Gnomad MID AF: 0.231

Gnomad NFE AF: 0.167

Gnomad OTH AF: 0.200

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

GnomAD4 genome AF: 0.195 AC: 29668 AN: 152006 Hom.: 3139 Cov.: 31 AF XY: 0.195 AC XY: 14490 AN XY: 74292

African (AFR) AF: 0.256 AC: 10619 AN: 41418

American (AMR) AF: 0.231 AC: 3523 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.185 AC: 641 AN: 3472

East Asian (EAS) AF: 0.0622 AC: 321 AN: 5162

South Asian (SAS) AF: 0.218 AC: 1051 AN: 4820

European-Finnish (FIN) AF: 0.148 AC: 1562 AN: 10564

Middle Eastern (MID) AF: 0.218 AC: 64 AN: 294

European-Non Finnish (NFE) AF: 0.167 AC: 11319 AN: 67970

Other (OTH) AF: 0.201 AC: 426 AN: 2116

Alfa AF: 0.181 Hom.: 4801

Bravo AF: 0.206

Asia WGS AF: 0.167 AC: 580 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	1.6
DANN	Benign	0.38
PhyloP100		-0.34
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: rs6838291; hg19: chr4-7917806;