7-156681085-T-TA

Position:

• chr7-156681085-T-TA

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_Moderate BA1

The NM_022458.4(LMBR1):​c.*2992_*2993insT variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.354 in 351,756 control chromosomes in the GnomAD database, including 8,186 homozygotes. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.28 (6996 hom., cov: 21)
  • Exomes 𝑓: 0.41 (1190 hom.)
• Consequence: LMBR1 NM_022458.4 3_prime_UTR
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.774

Genes affected

LMBR1 (HGNC:13243): (limb development membrane protein 1) This gene encodes a member of the LMBR1-like membrane protein family. Another member of this protein family has been shown to be a lipocalin transmembrane receptor. A highly conserved, cis-acting regulatory module for the sonic hedgehog gene is located within an intron of this gene. Consequently, disruption of this genic region can alter sonic hedgehog expression and affect limb patterning, but it is not known if this gene functions directly in limb development. Mutations and chromosomal deletions and rearrangements in this genic region are associated with acheiropody and preaxial polydactyly, which likely result from altered sonic hedgehog expression. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -10 ACMG points.

• BP6: Variant 7-156681085-T-TA is Benign according to our data. Variant chr7-156681085-T-TA is described in ClinVar as [Benign]. Clinvar id is 359369.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.378 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
LMBR1	NM_022458.4	c.*2992_*2993insT		3_prime_UTR_variant	17/17	ENST00000353442.10	NP_071903.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
LMBR1	ENST00000353442.10	c.*2992_*2993insT		3_prime_UTR_variant	17/17	1	NM_022458.4	ENSP00000326604	P1
LMBR1	ENST00000430825.3	n.266-512_266-511insT		intron_variant, non_coding_transcript_variant		5

Frequencies

GnomAD3 genomes AF: 0.279 AC: 41424 AN: 148572 Hom.: 6997 Cov.: 21

Gnomad AFR AF: 0.0810

Gnomad AMI AF: 0.555

Gnomad AMR AF: 0.311

Gnomad ASJ AF: 0.443

Gnomad EAS AF: 0.0758

Gnomad SAS AF: 0.344

Gnomad FIN AF: 0.317

Gnomad MID AF: 0.415

Gnomad NFE AF: 0.382

Gnomad OTH AF: 0.316

GnomAD4 exome AF: 0.410 AC: 83252 AN: 203092 Hom.: 1190 Cov.: 0 AF XY: 0.413 AC XY: 48314 AN XY: 117056

Gnomad4 AFR exome AF: 0.238

Gnomad4 AMR exome AF: 0.322

Gnomad4 ASJ exome AF: 0.435

Gnomad4 EAS exome AF: 0.249

Gnomad4 SAS exome AF: 0.421

Gnomad4 FIN exome AF: 0.409

Gnomad4 NFE exome AF: 0.430

Gnomad4 OTH exome AF: 0.412

GnomAD4 genome AF: 0.279 AC: 41428 AN: 148664 Hom.: 6996 Cov.: 21 AF XY: 0.276 AC XY: 20031 AN XY: 72488

Gnomad4 AFR AF: 0.0808

Gnomad4 AMR AF: 0.310

Gnomad4 ASJ AF: 0.443

Gnomad4 EAS AF: 0.0756

Gnomad4 SAS AF: 0.345

Gnomad4 FIN AF: 0.317

Gnomad4 NFE AF: 0.382

Gnomad4 OTH AF: 0.319

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

Triphalangeal thumb-polysyndactyly syndrome Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jun 14, 2016

- -

Computational scores

Source: dbNSFP v4.3

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: rs71838136; hg19: chr7-156473779;