7-156681085-TA-TAAA

Variant names:

• chr7-156681085-T-TAA
• rs71838136
• NM_022458.4:c.*2991_*2992dupTT

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BS1

The NM_022458.4(LMBR1):​c.*2991_*2992dupTT variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0174 in 371,968 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.00015 (0 hom., cov: 21)
  • Exomes 𝑓: 0.029 (0 hom.)
• Consequence: LMBR1 NM_022458.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• 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 Likely_benign. Variant got -4 ACMG points.

• BS1: Variant frequency is greater than expected in population nfe. gnomad4_exome allele frequency = 0.0289 (6439/223154) while in subpopulation NFE AF= 0.0321 (4024/125386). AF 95% confidence interval is 0.0313. There are 0 homozygotes in gnomad4_exome. There are 3632 alleles in male gnomad4_exome subpopulation. Median coverage is 0. This position pass quality control queck.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LMBR1	NM_022458.4	c.*2991_*2992dupTT		3_prime_UTR_variant	Exon 17 of 17	ENST00000353442.10	NP_071903.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
LMBR1	ENST00000353442	c.*2991_*2992dupTT		3_prime_UTR_variant	Exon 17 of 17	1	NM_022458.4	ENSP00000326604.7
LMBR1	ENST00000430825.3	n.266-513_266-512dupTT		intron_variant	Intron 1 of 4	5

Frequencies

GnomAD3 genomes AF: 0.000155 AC: 23 AN: 148722 Hom.: 0 Cov.: 21

Gnomad AFR AF: 0.0000495

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000669

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000391

Gnomad SAS AF: 0.000211

Gnomad FIN AF: 0.000310

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000194

Gnomad OTH AF: 0.000487

GnomAD4 exome AF: 0.0289 AC: 6439 AN: 223154 Hom.: 0 Cov.: 0 AF XY: 0.0281 AC XY: 3632 AN XY: 129394

Gnomad4 AFR exome AF: 0.00567

Gnomad4 AMR exome AF: 0.0234

Gnomad4 ASJ exome AF: 0.0352

Gnomad4 EAS exome AF: 0.00653

Gnomad4 SAS exome AF: 0.0304

Gnomad4 FIN exome AF: 0.0167

Gnomad4 NFE exome AF: 0.0321

Gnomad4 OTH exome AF: 0.0265

GnomAD4 genome AF: 0.000155 AC: 23 AN: 148814 Hom.: 0 Cov.: 21 AF XY: 0.000110 AC XY: 8 AN XY: 72592

Gnomad4 AFR AF: 0.0000494

Gnomad4 AMR AF: 0.0000668

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.000392

Gnomad4 SAS AF: 0.000211

Gnomad4 FIN AF: 0.000310

Gnomad4 NFE AF: 0.000194

Gnomad4 OTH AF: 0.000482

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Splicing

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;