rs4692589

Variant names:

• chr4-170014094-A-G
• rs4692589
• NM_021647.8:c.-133-8084T>C

Variant summary

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

The NM_021647.8(MFAP3L):​c.-133-8084T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.446 in 152,002 control chromosomes in the GnomAD database, including 15,356 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 0.45 (15356 hom., cov: 33)
• Consequence: MFAP3L NM_021647.8 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.99
• Publications: 9 publications found

Genes affected

MFAP3L (HGNC:29083): (microfibril associated protein 3 like) Located in several cellular components, including cell junction; nucleoplasm; and plasma membrane. [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=-0.88).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.695 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MFAP3L	NM_021647.8	c.-133-8084T>C		intron_variant	Intron 1 of 2	ENST00000361618.4	NP_067679.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MFAP3L	ENST00000361618.4	c.-133-8084T>C		intron_variant	Intron 1 of 2	1	NM_021647.8	ENSP00000354583.3

Frequencies

GnomAD3 genomes AF: 0.446 AC: 67690 AN: 151884 Hom.: 15342 Cov.: 33

Gnomad AFR AF: 0.462

Gnomad AMI AF: 0.449

Gnomad AMR AF: 0.469

Gnomad ASJ AF: 0.426

Gnomad EAS AF: 0.714

Gnomad SAS AF: 0.424

Gnomad FIN AF: 0.369

Gnomad MID AF: 0.478

Gnomad NFE AF: 0.424

Gnomad OTH AF: 0.466

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

GnomAD4 genome AF: 0.446 AC: 67745 AN: 152002 Hom.: 15356 Cov.: 33 AF XY: 0.444 AC XY: 32987 AN XY: 74282

African (AFR) AF: 0.462 AC: 19162 AN: 41456

American (AMR) AF: 0.469 AC: 7161 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.426 AC: 1476 AN: 3466

East Asian (EAS) AF: 0.714 AC: 3689 AN: 5168

South Asian (SAS) AF: 0.424 AC: 2044 AN: 4824

European-Finnish (FIN) AF: 0.369 AC: 3897 AN: 10552

Middle Eastern (MID) AF: 0.469 AC: 138 AN: 294

European-Non Finnish (NFE) AF: 0.424 AC: 28775 AN: 67940

Other (OTH) AF: 0.471 AC: 994 AN: 2110

Alfa AF: 0.449 Hom.: 5283

Bravo AF: 0.459

Asia WGS AF: 0.574 AC: 1993 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	7.9
DANN	Benign	0.36
PhyloP100		2.0
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: rs4692589; hg19: chr4-170935245;