4-7772941-G-C

Variant names:

• chr4-7772941-G-C
• rs144263460
• NM_001134647.2:c.2132C>G

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001134647.2(AFAP1):​c.2132C>G​(p.Ala711Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. A711V) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 33)
• Consequence: AFAP1 NM_001134647.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.71
• Publications: 0 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: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.109813124).

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.2132C>G	p.Ala711Gly	missense	Exon 16 of 18	NP_001128119.1	Q8N556-2
	AFAP1	NM_001371090.1		c.1880C>G	p.Ala627Gly	missense	Exon 14 of 16	NP_001358019.1	Q8N556-1
	AFAP1	NM_001371091.1		c.1880C>G	p.Ala627Gly	missense	Exon 16 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.2132C>G	p.Ala711Gly	missense	Exon 16 of 18	ENSP00000410689.1	Q8N556-2
	AFAP1	ENST00000360265.9	TSL:1	c.1880C>G	p.Ala627Gly	missense	Exon 14 of 16	ENSP00000353402.4	Q8N556-1
	AFAP1-AS1	ENST00000608442.2	TSL:1	n.821G>C		non_coding_transcript_exon	Exon 2 of 2

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD2 exomes AF: 0.00000401 AC: 1 AN: 249514 AF XY: 0.00

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00000890

Gnomad OTH exome AF: 0.00

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 33

ExAC AF: 0.00000824 AC: 1

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.081
BayesDel_addAF	Benign	-0.22	T
BayesDel_noAF	Benign	-0.56
CADD	Benign	20
DANN	Benign	0.92
DEOGEN2	Benign	0.020	T
Eigen	Benign	-0.52
Eigen_PC	Benign	-0.49
FATHMM_MKL	Benign	0.41	N
LIST_S2	Benign	0.79	T
M_CAP	Benign	0.013	T
MetaRNN	Benign	0.11	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.9	L
PhyloP100		2.7
PrimateAI	Benign	0.28	T
PROVEAN	Benign	-1.2	N
REVEL	Benign	0.042
Sift	Benign	0.31	T
Sift4G	Benign	0.26	T
Polyphen		0.13	B
Vest4		0.25
MutPred		0.22		Gain of glycosylation at S631 (P = 0.0018)
MVP		0.28
MPC		0.090
ClinPred		0.14	T
GERP RS		4.0
Varity_R		0.13
gMVP		0.029
Mutation Taster		=95/5	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		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: rs144263460; hg19: chr4-7774668;