chr11-64205924-G-A

Variant names:

• chr11-64205924-G-A
• rs1011219
• NM_001382448.1:c.-201G>A

Variant summary

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

The NM_001382448.1(FERMT3):​c.-201G>A variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.111 in 152,288 control chromosomes in the GnomAD database, including 1,168 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 0.11 (1168 hom., cov: 33)
• Consequence: FERMT3 NM_001382448.1 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.62
• Publications: 20 publications found

Genes affected

FERMT3 (HGNC:23151): (FERM domain containing kindlin 3) Kindlins are a small family of proteins that mediate protein-protein interactions involved in integrin activation and thereby have a role in cell adhesion, migration, differentiation, and proliferation. The protein encoded by this gene has a key role in the regulation of hemostasis and thrombosis. This protein may also help maintain the membrane skeleton of erythrocytes. Mutations in this gene cause the autosomal recessive leukocyte adhesion deficiency syndrome-III (LAD-III). Alternative splicing results in multiple transcript variants encoding distinct isoforms. [provided by RefSeq, Jan 2010]

FERMT3 Gene-Disease associations (from GenCC):

• leukocyte adhesion deficiency 3

  Inheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Labcorp Genetics (formerly Invitae), Genomics England PanelApp, Orphanet, ClinGen

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.95).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.159 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FERMT3	NM_001382448.1	c.-201G>A		5_prime_UTR_variant	Exon 1 of 16		NP_001369377.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FERMT3	ENST00000698852.1	c.-1441G>A		upstream_gene_variant				ENSP00000513984.1

Frequencies

GnomAD3 genomes AF: 0.111 AC: 16866 AN: 152170 Hom.: 1168 Cov.: 33

Gnomad AFR AF: 0.0440

Gnomad AMI AF: 0.150

Gnomad AMR AF: 0.0894

Gnomad ASJ AF: 0.0760

Gnomad EAS AF: 0.0960

Gnomad SAS AF: 0.0763

Gnomad FIN AF: 0.114

Gnomad MID AF: 0.0538

Gnomad NFE AF: 0.161

Gnomad OTH AF: 0.101

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

GnomAD4 genome AF: 0.111 AC: 16873 AN: 152288 Hom.: 1168 Cov.: 33 AF XY: 0.108 AC XY: 8032 AN XY: 74458

African (AFR) AF: 0.0441 AC: 1833 AN: 41552

American (AMR) AF: 0.0894 AC: 1369 AN: 15306

Ashkenazi Jewish (ASJ) AF: 0.0760 AC: 264 AN: 3472

East Asian (EAS) AF: 0.0959 AC: 496 AN: 5174

South Asian (SAS) AF: 0.0768 AC: 371 AN: 4830

European-Finnish (FIN) AF: 0.114 AC: 1210 AN: 10620

Middle Eastern (MID) AF: 0.0578 AC: 17 AN: 294

European-Non Finnish (NFE) AF: 0.161 AC: 10965 AN: 68012

Other (OTH) AF: 0.0997 AC: 211 AN: 2116

Alfa AF: 0.131 Hom.: 1634

Bravo AF: 0.107

Asia WGS AF: 0.0850 AC: 294 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	1.2
DANN	Benign	0.67
PhyloP100		-2.6

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs1011219; hg19: chr11-63973396;