5-149274168-A-G

Variant names:

• chr5-149274168-A-G
• rs4705335
• NM_152406.4:c.16+2184A>G

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+2184A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.847 in 152,202 control chromosomes in the GnomAD database, including 54,682 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 0.85 (54682 hom., cov: 32)
• Consequence: AFAP1L1 NM_152406.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.26
• Publications: 1 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]

ENSG00000253406 (HGNC:):

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.942 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+2184A>G		intron	N/A	NP_689619.1
	AFAP1L1	NM_001323062.2		c.16+2184A>G		intron	N/A	NP_001309991.1
	AFAP1L1	NM_001146337.3		c.16+2184A>G		intron	N/A	NP_001139809.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	AFAP1L1	ENST00000296721.9	TSL:1 MANE Select	c.16+2184A>G		intron	N/A	ENSP00000296721.4
	AFAP1L1	ENST00000515000.1	TSL:1	c.16+2184A>G		intron	N/A	ENSP00000424427.1
	AFAP1L1	ENST00000455574.6	TSL:1	n.114+2184A>G		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.847 AC: 128798 AN: 152084 Hom.: 54639 Cov.: 32

Gnomad AFR AF: 0.856

Gnomad AMI AF: 0.857

Gnomad AMR AF: 0.866

Gnomad ASJ AF: 0.792

Gnomad EAS AF: 0.965

Gnomad SAS AF: 0.875

Gnomad FIN AF: 0.834

Gnomad MID AF: 0.810

Gnomad NFE AF: 0.831

Gnomad OTH AF: 0.831

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

GnomAD4 genome AF: 0.847 AC: 128898 AN: 152202 Hom.: 54682 Cov.: 32 AF XY: 0.847 AC XY: 63026 AN XY: 74398

African (AFR) AF: 0.856 AC: 35556 AN: 41536

American (AMR) AF: 0.866 AC: 13248 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.792 AC: 2748 AN: 3470

East Asian (EAS) AF: 0.965 AC: 4983 AN: 5166

South Asian (SAS) AF: 0.876 AC: 4228 AN: 4824

European-Finnish (FIN) AF: 0.834 AC: 8822 AN: 10582

Middle Eastern (MID) AF: 0.806 AC: 237 AN: 294

European-Non Finnish (NFE) AF: 0.831 AC: 56546 AN: 68014

Other (OTH) AF: 0.829 AC: 1750 AN: 2112

Alfa AF: 0.836 Hom.: 62435

Bravo AF: 0.855

Asia WGS AF: 0.892 AC: 3102 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	0.21
DANN	Benign	0.76
PhyloP100		-1.3
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: rs4705335; hg19: chr5-148653731; COSMIC: COSV57044448;