rs34856996

Variant names:

• chr11-64117089-G-A
• rs34856996
• NM_013280.5:c.822G>A

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BA1

The NM_013280.5(FLRT1):​c.822G>A​(p.Lys274Lys) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.05 in 1,603,572 control chromosomes in the GnomAD database, including 2,244 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.040 (167 hom., cov: 34)
  • Exomes 𝑓: 0.051 (2077 hom.)
• Consequence: FLRT1 NM_013280.5 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 1.84
• Publications: 9 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]

ACMG classification

Our verdict: Benign. The variant received -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.55).
• BP6: Variant 11-64117089-G-A is Benign according to our data. Variant chr11-64117089-G-A is described in ClinVar as Benign. ClinVar VariationId is 461805.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=1.84 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0618 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FLRT1	NM_013280.5	c.822G>A	p.Lys274Lys	synonymous_variant	Exon 3 of 3	ENST00000682287.1	NP_037412.2
MACROD1	NM_014067.4	c.517+34150C>T		intron_variant	Intron 3 of 10	ENST00000255681.7	NP_054786.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FLRT1	ENST00000682287.1	c.822G>A	p.Lys274Lys	synonymous_variant	Exon 3 of 3		NM_013280.5	ENSP00000507207.1
MACROD1	ENST00000255681.7	c.517+34150C>T		intron_variant	Intron 3 of 10	1	NM_014067.4	ENSP00000255681.6

Frequencies

GnomAD3 genomes AF: 0.0404 AC: 6156 AN: 152224 Hom.: 167 Cov.: 34

Gnomad AFR AF: 0.0107

Gnomad AMI AF: 0.0504

Gnomad AMR AF: 0.0347

Gnomad ASJ AF: 0.0533

Gnomad EAS AF: 0.000384

Gnomad SAS AF: 0.0192

Gnomad FIN AF: 0.0404

Gnomad MID AF: 0.0506

Gnomad NFE AF: 0.0633

Gnomad OTH AF: 0.0489

GnomAD2 exomes AF: 0.0394 AC: 8949 AN: 227212 AF XY: 0.0392

Gnomad AFR exome AF: 0.00892

Gnomad AMR exome AF: 0.0212

Gnomad ASJ exome AF: 0.0552

Gnomad EAS exome AF: 0.000122

Gnomad FIN exome AF: 0.0425

Gnomad NFE exome AF: 0.0589

Gnomad OTH exome AF: 0.0469

GnomAD4 exome AF: 0.0510 AC: 74034 AN: 1451230 Hom.: 2077 Cov.: 90 AF XY: 0.0501 AC XY: 36130 AN XY: 721114

African (AFR) AF: 0.00777 AC: 258 AN: 33204

American (AMR) AF: 0.0220 AC: 935 AN: 42590

Ashkenazi Jewish (ASJ) AF: 0.0569 AC: 1472 AN: 25870

East Asian (EAS) AF: 0.000102 AC: 4 AN: 39068

South Asian (SAS) AF: 0.0186 AC: 1583 AN: 85050

European-Finnish (FIN) AF: 0.0445 AC: 2341 AN: 52570

Middle Eastern (MID) AF: 0.0383 AC: 220 AN: 5750

European-Non Finnish (NFE) AF: 0.0584 AC: 64624 AN: 1107106

Other (OTH) AF: 0.0433 AC: 2597 AN: 60022

GnomAD4 genome AF: 0.0404 AC: 6150 AN: 152342 Hom.: 167 Cov.: 34 AF XY: 0.0395 AC XY: 2943 AN XY: 74500

African (AFR) AF: 0.0107 AC: 443 AN: 41578

American (AMR) AF: 0.0345 AC: 528 AN: 15308

Ashkenazi Jewish (ASJ) AF: 0.0533 AC: 185 AN: 3468

East Asian (EAS) AF: 0.000385 AC: 2 AN: 5190

South Asian (SAS) AF: 0.0192 AC: 93 AN: 4834

European-Finnish (FIN) AF: 0.0404 AC: 429 AN: 10620

Middle Eastern (MID) AF: 0.0476 AC: 14 AN: 294

European-Non Finnish (NFE) AF: 0.0633 AC: 4309 AN: 68028

Other (OTH) AF: 0.0479 AC: 101 AN: 2110

Alfa AF: 0.0566 Hom.: 538

Bravo AF: 0.0380

Asia WGS AF: 0.00982 AC: 34 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

Peripheral neuropathy Benign:1

Jan 06, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

not provided Benign:1

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.55
CADD	Benign	9.4
DANN	Benign	0.91
PhyloP100		1.8
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.8
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs34856996; hg19: chr11-63884561;