4-7776797-G-T

Variant names:

• chr4-7776797-G-T
• rs10516187
• NM_001134647.2:c.1898-1894C>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.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
• Publications: 4 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]

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

Our verdict: Benign. The variant received -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.

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.1898-1894C>A		intron	N/A	NP_001128119.1	Q8N556-2
	AFAP1	NM_001371090.1		c.1646-1894C>A		intron	N/A	NP_001358019.1	Q8N556-1
	AFAP1	NM_001371091.1		c.1646-1894C>A		intron	N/A	NP_001358020.1	Q8N556-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	AFAP1	ENST00000420658.6	TSL:2 MANE Select	c.1898-1894C>A		intron	N/A	ENSP00000410689.1	Q8N556-2
	AFAP1	ENST00000360265.9	TSL:1	c.1646-1894C>A		intron	N/A	ENSP00000353402.4	Q8N556-1
	AFAP1-AS1	ENST00000608442.2	TSL:1	n.4677G>T		non_coding_transcript_exon	Exon 2 of 2

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

African (AFR) AC: 0 AN: 0

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 2

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AC: 0 AN: 0

Other (OTH) AC: 0 AN: 0

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

African (AFR) AF: 0.221 AC: 9173 AN: 41450

American (AMR) AF: 0.320 AC: 4881 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.196 AC: 681 AN: 3468

East Asian (EAS) AF: 0.756 AC: 3904 AN: 5162

South Asian (SAS) AF: 0.397 AC: 1912 AN: 4818

European-Finnish (FIN) AF: 0.269 AC: 2832 AN: 10542

Middle Eastern (MID) AF: 0.194 AC: 57 AN: 294

European-Non Finnish (NFE) AF: 0.182 AC: 12358 AN: 67986

Other (OTH) AF: 0.229 AC: 485 AN: 2114

Alfa AF: 0.205 Hom.: 1894

Bravo AF: 0.240

Asia WGS AF: 0.506 AC: 1760 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.34
DANN	Benign	0.78
PhyloP100		-0.94
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs10516187; hg19: chr4-7778524;