rs12657199

Variant names:

• chr5-149277363-G-T
• rs12657199
• NM_152406.4:c.16+5379G>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_152406.4(AFAP1L1):​c.16+5379G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.339 in 152,082 control chromosomes in the GnomAD database, including 9,694 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 0.34 (9694 hom., cov: 32)
• Consequence: AFAP1L1 NM_152406.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.471
• Publications: 5 publications found

Genes affected

AFAP1L1 (HGNC:26714): (actin filament associated protein 1 like 1) Predicted to enable SH3 domain binding activity. Predicted to be located in cell junction; cell projection; and podosome. Predicted to be active in cytosol. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.513 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_152406.4. 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
	AFAP1L1	NM_152406.4	MANE Select	c.16+5379G>T		intron	N/A	NP_689619.1	Q8TED9-1
	AFAP1L1	NM_001323062.2		c.16+5379G>T		intron	N/A	NP_001309991.1
	AFAP1L1	NM_001146337.3		c.16+5379G>T		intron	N/A	NP_001139809.1	Q8TED9-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	AFAP1L1	ENST00000296721.9	TSL:1 MANE Select	c.16+5379G>T		intron	N/A	ENSP00000296721.4	Q8TED9-1
	AFAP1L1	ENST00000515000.1	TSL:1	c.16+5379G>T		intron	N/A	ENSP00000424427.1	Q8TED9-2
	AFAP1L1	ENST00000455574.6	TSL:1	n.114+5379G>T		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.339 AC: 51521 AN: 151964 Hom.: 9672 Cov.: 32

Gnomad AFR AF: 0.170

Gnomad AMI AF: 0.354

Gnomad AMR AF: 0.438

Gnomad ASJ AF: 0.296

Gnomad EAS AF: 0.529

Gnomad SAS AF: 0.374

Gnomad FIN AF: 0.385

Gnomad MID AF: 0.263

Gnomad NFE AF: 0.398

Gnomad OTH AF: 0.327

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

GnomAD4 genome AF: 0.339 AC: 51572 AN: 152082 Hom.: 9694 Cov.: 32 AF XY: 0.341 AC XY: 25323 AN XY: 74336

African (AFR) AF: 0.170 AC: 7062 AN: 41512

American (AMR) AF: 0.440 AC: 6717 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.296 AC: 1028 AN: 3468

East Asian (EAS) AF: 0.529 AC: 2730 AN: 5160

South Asian (SAS) AF: 0.375 AC: 1810 AN: 4822

European-Finnish (FIN) AF: 0.385 AC: 4064 AN: 10550

Middle Eastern (MID) AF: 0.255 AC: 75 AN: 294

European-Non Finnish (NFE) AF: 0.398 AC: 27067 AN: 67972

Other (OTH) AF: 0.329 AC: 696 AN: 2116

Alfa AF: 0.351 Hom.: 2299

Bravo AF: 0.339

Asia WGS AF: 0.445 AC: 1551 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.072
DANN	Benign	0.42
PhyloP100		-0.47
Mutation Taster		=100/0	polymorphism (auto)

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: rs12657199; hg19: chr5-148656926;