rs1438692

Variant names:

• chr5-149280101-G-A
• rs1438692
• NM_152406.4:c.16+8117G>A

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+8117G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.371 in 152,100 control chromosomes in the GnomAD database, including 10,894 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 0.37 (10894 hom., cov: 32)
• Consequence: AFAP1L1 NM_152406.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.767
• Publications: 8 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 = 0.549 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
AFAP1L1	NM_152406.4	c.16+8117G>A		intron_variant	Intron 1 of 18	ENST00000296721.9	NP_689619.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
AFAP1L1	ENST00000296721.9	c.16+8117G>A		intron_variant	Intron 1 of 18	1	NM_152406.4	ENSP00000296721.4
AFAP1L1	ENST00000515000.1	c.16+8117G>A		intron_variant	Intron 1 of 17	1		ENSP00000424427.1
AFAP1L1	ENST00000455574.6	n.114+8117G>A		intron_variant	Intron 1 of 8	1
AFAP1L1	ENST00000522492.1	n.90+8117G>A		intron_variant	Intron 1 of 7	3

Frequencies

GnomAD3 genomes AF: 0.371 AC: 56347 AN: 151982 Hom.: 10871 Cov.: 32

Gnomad AFR AF: 0.273

Gnomad AMI AF: 0.354

Gnomad AMR AF: 0.451

Gnomad ASJ AF: 0.293

Gnomad EAS AF: 0.567

Gnomad SAS AF: 0.405

Gnomad FIN AF: 0.384

Gnomad MID AF: 0.269

Gnomad NFE AF: 0.398

Gnomad OTH AF: 0.353

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

GnomAD4 genome AF: 0.371 AC: 56411 AN: 152100 Hom.: 10894 Cov.: 32 AF XY: 0.372 AC XY: 27644 AN XY: 74350

African (AFR) AF: 0.273 AC: 11331 AN: 41502

American (AMR) AF: 0.452 AC: 6913 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.293 AC: 1016 AN: 3468

East Asian (EAS) AF: 0.566 AC: 2924 AN: 5162

South Asian (SAS) AF: 0.406 AC: 1955 AN: 4812

European-Finnish (FIN) AF: 0.384 AC: 4066 AN: 10576

Middle Eastern (MID) AF: 0.262 AC: 76 AN: 290

European-Non Finnish (NFE) AF: 0.398 AC: 27057 AN: 67972

Other (OTH) AF: 0.355 AC: 751 AN: 2114

Alfa AF: 0.392 Hom.: 53702

Bravo AF: 0.374

Asia WGS AF: 0.504 AC: 1758 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	0.14
DANN	Benign	0.58
PhyloP100		-0.77
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: rs1438692; hg19: chr5-148659664;