rs641811

Positions:

• chr11-64102124-G-A

Variant summary

Our verdict is Benign. Variant got -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

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

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
FLRT1	NM_013280.5	c.-1037-1070G>A		intron_variant		ENST00000682287.1	NP_037412.2
MACROD1	NM_014067.4	c.517+49115C>T		intron_variant		ENST00000255681.7	NP_054786.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
FLRT1	ENST00000682287.1	c.-1037-1070G>A		intron_variant			NM_013280.5	ENSP00000507207.1
MACROD1	ENST00000255681.7	c.517+49115C>T		intron_variant		1	NM_014067.4	ENSP00000255681.6

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

Gnomad4 AFR AF: 0.433

Gnomad4 AMR AF: 0.253

Gnomad4 ASJ AF: 0.124

Gnomad4 EAS AF: 0.244

Gnomad4 SAS AF: 0.234

Gnomad4 FIN AF: 0.171

Gnomad4 NFE AF: 0.213

Gnomad4 OTH AF: 0.231

Alfa AF: 0.217 Hom.: 6291

Bravo AF: 0.286

Asia WGS AF: 0.236 AC: 822 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.29
CADD	Benign	15
DANN	Benign	0.85

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

Publications

LitVar

Other links and lift over

dbSNP: rs641811; hg19: chr11-63869596;