4-7763774-G-A

Variant names:

• chr4-7763774-G-A
• rs114329356
• NM_001134647.2:c.2436C>T

Variant summary

Our verdict is Benign. The variant received -11 ACMG points: 0P and 11B. BP4_Strong BP6_Moderate BP7 BS2

The NM_001134647.2(AFAP1):​c.2436C>T​(p.Asn812Asn) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00706 in 1,551,574 control chromosomes in the GnomAD database, including 42 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0045 (1 hom., cov: 33)
  • Exomes 𝑓: 0.0073 (41 hom.)
• Consequence: AFAP1 NM_001134647.2 synonymous
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.336
• Publications: 3 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 -11 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.68).
• BP6: Variant 4-7763774-G-A is Benign according to our data. Variant chr4-7763774-G-A is described in ClinVar as Likely_benign. ClinVar VariationId is 2654639.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=-0.336 with no splicing effect.
• BS2: High Homozygotes in GnomAdExome4 at 41 AR gene

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.2436C>T	p.Asn812Asn	synonymous	Exon 18 of 18	NP_001128119.1	Q8N556-2
	AFAP1	NM_001371090.1		c.2184C>T	p.Asn728Asn	synonymous	Exon 16 of 16	NP_001358019.1	Q8N556-1
	AFAP1	NM_001371091.1		c.2184C>T	p.Asn728Asn	synonymous	Exon 18 of 18	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.2436C>T	p.Asn812Asn	synonymous	Exon 18 of 18	ENSP00000410689.1	Q8N556-2
	AFAP1	ENST00000360265.9	TSL:1	c.2184C>T	p.Asn728Asn	synonymous	Exon 16 of 16	ENSP00000353402.4	Q8N556-1
	AFAP1-AS1	ENST00000608442.2	TSL:1	n.84-8430G>A		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.00451 AC: 686 AN: 152116 Hom.: 1 Cov.: 33

Gnomad AFR AF: 0.00171

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00393

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000622

Gnomad FIN AF: 0.000754

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00784

Gnomad OTH AF: 0.00526

GnomAD2 exomes AF: 0.00474 AC: 738 AN: 155666 AF XY: 0.00477

Gnomad AFR exome AF: 0.00217

Gnomad AMR exome AF: 0.00488

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.000975

Gnomad NFE exome AF: 0.00887

Gnomad OTH exome AF: 0.00542

GnomAD4 exome AF: 0.00734 AC: 10268 AN: 1399340 Hom.: 41 Cov.: 31 AF XY: 0.00707 AC XY: 4881 AN XY: 690206

African (AFR) AF: 0.00111 AC: 35 AN: 31594

American (AMR) AF: 0.00507 AC: 181 AN: 35726

Ashkenazi Jewish (ASJ) AF: 0.0000794 AC: 2 AN: 25180

East Asian (EAS) AF: 0.00 AC: 0 AN: 35744

South Asian (SAS) AF: 0.00140 AC: 111 AN: 79228

European-Finnish (FIN) AF: 0.00114 AC: 56 AN: 49306

Middle Eastern (MID) AF: 0.00105 AC: 6 AN: 5696

European-Non Finnish (NFE) AF: 0.00885 AC: 9553 AN: 1078868

Other (OTH) AF: 0.00559 AC: 324 AN: 57998

GnomAD4 genome AF: 0.00451 AC: 686 AN: 152234 Hom.: 1 Cov.: 33 AF XY: 0.00441 AC XY: 328 AN XY: 74428

African (AFR) AF: 0.00171 AC: 71 AN: 41522

American (AMR) AF: 0.00392 AC: 60 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5182

South Asian (SAS) AF: 0.000623 AC: 3 AN: 4818

European-Finnish (FIN) AF: 0.000754 AC: 8 AN: 10608

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.00784 AC: 533 AN: 68016

Other (OTH) AF: 0.00520 AC: 11 AN: 2114

Alfa AF: 0.00590 Hom.: 3

Bravo AF: 0.00485

Asia WGS AF: 0.00144 AC: 5 AN: 3478

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.68
CADD	Benign	2.1
DANN	Benign	0.39
PhyloP100		-0.34
Mutation Taster		=100/0	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.16		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: rs114329356; hg19: chr4-7765501;