11-62671374-G-A

Variant names:

• chr11-62671374-G-A
• rs3809079
• NM_024099.5:c.-11+190C>T

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_001394599.1(LBHD1):​c.374C>T​(p.Ala125Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.286 in 1,284,282 control chromosomes in the GnomAD database, including 54,666 homozygotes. In-silico tool predicts a benign outcome for this variant. 5/5 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.24 (4799 hom., cov: 32)
  • Exomes 𝑓: 0.29 (49867 hom.)
• Consequence: LBHD1 NM_001394599.1 missense
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.803
• Publications: 20 publications found

Genes affected

LBHD1 (HGNC:28351): (LBH domain containing 1) This gene shares three exons in common with another gene, chromosome 11 open reading frame 98 (GeneID:102288414), but the encoded protein uses a reading frame that is different from that of the chromosome 11 open reading frame 98 gene. [provided by RefSeq, Nov 2017]

UQCC3 (HGNC:34399): (ubiquinol-cytochrome c reductase complex assembly factor 3) Complex III is a mitochondrial inner membrane protein complex that transfers electrons from ubiquinol to cytochrome c. This gene encodes a protein that functions in complex III assembly. Mutations in this gene result in Mitochondrial complex III deficiency, nuclear type 9. [provided by RefSeq, Dec 2014]

UQCC3 Gene-Disease associations (from GenCC):

• mitochondrial complex III deficiency

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.78).
• BP6: Variant 11-62671374-G-A is Benign according to our data. Variant chr11-62671374-G-A is described in ClinVar as Benign. ClinVar VariationId is 1226789.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.3 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001394599.1. 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
	LBHD1	NM_024099.5	MANE Select	c.-11+190C>T		intron	N/A	NP_077004.2
	LBHD1	NM_001394599.1		c.374C>T	p.Ala125Val	missense	Exon 1 of 7	NP_001381528.1
	LBHD1	NM_001394601.1		c.374C>T	p.Ala125Val	missense	Exon 1 of 5	NP_001381530.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LBHD1	ENST00000354588.8	TSL:1 MANE Select	c.-11+190C>T		intron	N/A	ENSP00000346600.3	Q9BQE6-2
	LBHD1	ENST00000431002.6	TSL:2	c.-1343C>T		5_prime_UTR	Exon 1 of 5	ENSP00000416856.2	Q9BQE6-1
	LBHD1	ENST00000532208.5	TSL:5	c.-269C>T		5_prime_UTR	Exon 1 of 7	ENSP00000436848.1	Q9BQE6-2

Frequencies

GnomAD3 genomes AF: 0.241 AC: 36661 AN: 151922 Hom.: 4796 Cov.: 32

Gnomad AFR AF: 0.176

Gnomad AMI AF: 0.216

Gnomad AMR AF: 0.231

Gnomad ASJ AF: 0.236

Gnomad EAS AF: 0.0734

Gnomad SAS AF: 0.201

Gnomad FIN AF: 0.207

Gnomad MID AF: 0.269

Gnomad NFE AF: 0.304

Gnomad OTH AF: 0.274

GnomAD2 exomes AF: 0.232 AC: 30633 AN: 132250 AF XY: 0.235

Gnomad AFR exome AF: 0.175

Gnomad AMR exome AF: 0.194

Gnomad ASJ exome AF: 0.233

Gnomad EAS exome AF: 0.0788

Gnomad FIN exome AF: 0.209

Gnomad NFE exome AF: 0.301

Gnomad OTH exome AF: 0.235

GnomAD4 exome AF: 0.292 AC: 330061 AN: 1132242 Hom.: 49867 Cov.: 22 AF XY: 0.288 AC XY: 160378 AN XY: 556268

African (AFR) AF: 0.168 AC: 4113 AN: 24498

American (AMR) AF: 0.191 AC: 5194 AN: 27202

Ashkenazi Jewish (ASJ) AF: 0.236 AC: 3792 AN: 16042

East Asian (EAS) AF: 0.0762 AC: 1025 AN: 13454

South Asian (SAS) AF: 0.204 AC: 15409 AN: 75582

European-Finnish (FIN) AF: 0.217 AC: 2919 AN: 13478

Middle Eastern (MID) AF: 0.250 AC: 1049 AN: 4204

European-Non Finnish (NFE) AF: 0.312 AC: 285675 AN: 916050

Other (OTH) AF: 0.261 AC: 10885 AN: 41732

GnomAD4 genome AF: 0.241 AC: 36678 AN: 152040 Hom.: 4799 Cov.: 32 AF XY: 0.236 AC XY: 17570 AN XY: 74296

African (AFR) AF: 0.176 AC: 7277 AN: 41448

American (AMR) AF: 0.231 AC: 3517 AN: 15240

Ashkenazi Jewish (ASJ) AF: 0.236 AC: 820 AN: 3472

East Asian (EAS) AF: 0.0734 AC: 380 AN: 5176

South Asian (SAS) AF: 0.201 AC: 972 AN: 4828

European-Finnish (FIN) AF: 0.207 AC: 2193 AN: 10584

Middle Eastern (MID) AF: 0.269 AC: 79 AN: 294

European-Non Finnish (NFE) AF: 0.304 AC: 20658 AN: 67976

Other (OTH) AF: 0.277 AC: 585 AN: 2110

Alfa AF: 0.283 Hom.: 16084

Bravo AF: 0.240

Asia WGS AF: 0.125 AC: 439 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.78
CADD	Benign	7.4
DANN	Benign	0.82
PhyloP100		0.80
PromoterAI		0.026	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.2
Mutation Taster		=300/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.060		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: rs3809079; hg19: chr11-62438846; COSMIC: COSV63473039; COSMIC: COSV63473039;