chr11-64102124-G-A

Variant names:

• chr11-64102124-G-A
• rs641811
• NM_013280.5:c.-1037-1070G>A

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_Moderate BA1

The NM_013280.5(FLRT1):​c.-1037-1070G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.274 in 152,132 control chromosomes in the GnomAD database, including 6,476 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 0.27 (6476 hom., cov: 32)
• Consequence: FLRT1 NM_013280.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.24
• Publications: 7 publications found

Genes affected

FLRT1 (HGNC:3760): (fibronectin leucine rich transmembrane protein 1) This gene encodes a member of the fibronectin leucine rich transmembrane protein (FLRT) family. The family members may function in cell adhesion and/or receptor signalling. Their protein structures resemble small leucine-rich proteoglycans found in the extracellular matrix. The encoded protein shares sequence similarity with two other family members, FLRT2 and FLRT3. This gene is expressed in kidney and brain. [provided by RefSeq, Jul 2008]

MACROD1 (HGNC:29598): (mono-ADP ribosylhydrolase 1) Enables ADP-ribosylglutamate hydrolase activity and deacetylase activity. Involved in cellular response to DNA damage stimulus; peptidyl-glutamate ADP-deribosylation; and purine nucleoside metabolic process. Located in nucleoplasm. [provided by Alliance of Genome Resources, Apr 2022]

ENSG00000256824 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.29).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.428 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_013280.5. 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
	FLRT1	NM_013280.5	MANE Select	c.-1037-1070G>A		intron	N/A	NP_037412.2
	MACROD1	NM_014067.4	MANE Select	c.517+49115C>T		intron	N/A	NP_054786.2
	FLRT1	NM_001384466.1		c.-1037-1070G>A		intron	N/A	NP_001371395.1	Q9NZU1-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FLRT1	ENST00000682287.1	MANE Select	c.-1037-1070G>A		intron	N/A	ENSP00000507207.1	Q9NZU1-2
	MACROD1	ENST00000255681.7	TSL:1 MANE Select	c.517+49115C>T		intron	N/A	ENSP00000255681.6	Q9BQ69
	FLRT1	ENST00000715990.1		c.-1121-1070G>A		intron	N/A	ENSP00000520551.1	Q9NZU1-1

Frequencies

GnomAD3 genomes AF: 0.274 AC: 41640 AN: 152014 Hom.: 6472 Cov.: 32

Gnomad AFR AF: 0.433

Gnomad AMI AF: 0.189

Gnomad AMR AF: 0.253

Gnomad ASJ AF: 0.124

Gnomad EAS AF: 0.244

Gnomad SAS AF: 0.235

Gnomad FIN AF: 0.171

Gnomad MID AF: 0.158

Gnomad NFE AF: 0.213

Gnomad OTH AF: 0.234

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

GnomAD4 genome AF: 0.274 AC: 41676 AN: 152132 Hom.: 6476 Cov.: 32 AF XY: 0.271 AC XY: 20147 AN XY: 74376

African (AFR) AF: 0.433 AC: 17969 AN: 41472

American (AMR) AF: 0.253 AC: 3874 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.124 AC: 430 AN: 3466

East Asian (EAS) AF: 0.244 AC: 1262 AN: 5176

South Asian (SAS) AF: 0.234 AC: 1128 AN: 4822

European-Finnish (FIN) AF: 0.171 AC: 1814 AN: 10596

Middle Eastern (MID) AF: 0.163 AC: 48 AN: 294

European-Non Finnish (NFE) AF: 0.213 AC: 14491 AN: 67992

Other (OTH) AF: 0.231 AC: 488 AN: 2112

Alfa AF: 0.235 Hom.: 13588

Bravo AF: 0.286

Asia WGS AF: 0.236 AC: 822 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.29
CADD	Benign	15
DANN	Benign	0.85
PhyloP100		1.2
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: rs641811; hg19: chr11-63869596;