chr4-7776797-G-T

Position:

• chr4-7776797-G-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001134647.2(AFAP1):​c.1898-1894C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.24 in 152,018 control chromosomes in the GnomAD database, including 5,392 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 0.24 (5392 hom., cov: 33)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: AFAP1 NM_001134647.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.945

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]

AFAP1-AS1 (HGNC:28141): (AFAP1 antisense RNA 1) This gene produces a long non-coding RNA that is overexpressed in tumor cells and may promote cancer cell metastasis. [provided by RefSeq, Dec 2017]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.736 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
AFAP1	NM_001134647.2	c.1898-1894C>A		intron_variant		ENST00000420658.6
AFAP1-AS1	NR_026892.1	n.4664G>T		non_coding_transcript_exon_variant	2/2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
AFAP1	ENST00000420658.6	c.1898-1894C>A		intron_variant		2	NM_001134647.2
AFAP1-AS1	ENST00000608442.2	n.4677G>T		non_coding_transcript_exon_variant	2/2	1

Frequencies

GnomAD3 genomes AF: 0.240 AC: 36496 AN: 151900 Hom.: 5384 Cov.: 33

Gnomad AFR AF: 0.221

Gnomad AMI AF: 0.255

Gnomad AMR AF: 0.319

Gnomad ASJ AF: 0.196

Gnomad EAS AF: 0.757

Gnomad SAS AF: 0.398

Gnomad FIN AF: 0.269

Gnomad MID AF: 0.193

Gnomad NFE AF: 0.182

Gnomad OTH AF: 0.230

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 2 Hom.: 0 Cov.: 0 AC XY: 0 AN XY: 0

Gnomad4 FIN exome AF: 0.00

GnomAD4 genome AF: 0.240 AC: 36515 AN: 152018 Hom.: 5392 Cov.: 33 AF XY: 0.250 AC XY: 18606 AN XY: 74290

Gnomad4 AFR AF: 0.221

Gnomad4 AMR AF: 0.320

Gnomad4 ASJ AF: 0.196

Gnomad4 EAS AF: 0.756

Gnomad4 SAS AF: 0.397

Gnomad4 FIN AF: 0.269

Gnomad4 NFE AF: 0.182

Gnomad4 OTH AF: 0.229

Alfa AF: 0.207 Hom.: 1736

Bravo AF: 0.240

Asia WGS AF: 0.506 AC: 1760 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.34
DANN	Benign	0.78

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		Details are displayed if max score is > 0.2

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

Publications

LitVar

Other links and lift over

dbSNP: rs10516187; hg19: chr4-7778524;