rs12657199

chr5-149277363-G-T

Variant summary

Our verdict is Benign. Variant got -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

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

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
AFAP1L1	NM_152406.4	c.16+5379G>T		intron_variant		ENST00000296721.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
AFAP1L1	ENST00000296721.9	c.16+5379G>T		intron_variant		1	NM_152406.4	P1
AFAP1L1	ENST00000515000.1	c.16+5379G>T		intron_variant		1
AFAP1L1	ENST00000455574.6	n.114+5379G>T		intron_variant, non_coding_transcript_variant		1
AFAP1L1	ENST00000522492.1	n.90+5379G>T		intron_variant, non_coding_transcript_variant		3

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

Gnomad4 AFR AF: 0.170

Gnomad4 AMR AF: 0.440

Gnomad4 ASJ AF: 0.296

Gnomad4 EAS AF: 0.529

Gnomad4 SAS AF: 0.375

Gnomad4 FIN AF: 0.385

Gnomad4 NFE AF: 0.398

Gnomad4 OTH AF: 0.329

Alfa AF: 0.355 Hom.: 2279

Bravo AF: 0.339

Asia WGS AF: 0.445 AC: 1551 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
Cadd	Benign	0.072
Dann	Benign	0.42

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

Publications

LitVar

Other links and lift over

dbSNP: rs12657199; hg19: chr5-148656926;