NM_178175.4:c.491G>A

Variant names:

• chrX-112631592-C-T
• rs370162233
• NM_178175.4:c.491G>A

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BP4_Moderate BP6_Moderate BS2

The NM_178175.4(LHFPL1):​c.491G>A​(p.Arg164Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000436 in 1,191,848 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 12 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R164W) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.000018 (0 hom., 0 hem., cov: 22)
  • Exomes 𝑓: 0.000046 (0 hom. 12 hem.)
• Consequence: LHFPL1 NM_178175.4 missense
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 1.54
• Publications: 1 publications found

Genes affected

LHFPL1 (HGNC:6587): (LHFPL tetraspan subfamily member 1) This gene is a member of the lipoma HMGIC fusion partner (LHFP) gene family, which is a subset of the superfamily of tetraspan transmembrane protein encoding genes. Mutations in one LHFP-like gene result in deafness in humans and mice, and a second LHFP-like gene is fused to a high-mobility group gene in a translocation-associated lipoma. Alternatively spliced transcript variants have been found, but their biological validity has not been determined. [provided by RefSeq, Jul 2008]

ACMG classification

Our verdict: Benign. The variant received -8 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.13783538).
• BP6: Variant X-112631592-C-T is Benign according to our data. Variant chrX-112631592-C-T is described in ClinVar as Likely_benign. ClinVar VariationId is 2405012.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High Hemizygotes in GnomAdExome4 at 12 gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_178175.4. 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
	LHFPL1	NM_178175.4	MANE Select	c.491G>A	p.Arg164Gln	missense	Exon 4 of 4	NP_835469.1	Q86WI0-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LHFPL1	ENST00000371968.8	TSL:1 MANE Select	c.491G>A	p.Arg164Gln	missense	Exon 4 of 4	ENSP00000361036.3	Q86WI0-1
	LHFPL1	ENST00000864007.1		c.491G>A	p.Arg164Gln	missense	Exon 4 of 4	ENSP00000534066.1
	LHFPL1	ENST00000864010.1		c.491G>A	p.Arg164Gln	missense	Exon 4 of 4	ENSP00000534070.1

Frequencies

GnomAD3 genomes AF: 0.0000179 AC: 2 AN: 111995 Hom.: 0 Cov.: 22

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000376

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000112 AC: 2 AN: 177933 AF XY: 0.00

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000251

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000463 AC: 50 AN: 1079853 Hom.: 0 Cov.: 28 AF XY: 0.0000345 AC XY: 12 AN XY: 347395

African (AFR) AF: 0.00 AC: 0 AN: 26120

American (AMR) AF: 0.00 AC: 0 AN: 34714

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 18934

East Asian (EAS) AF: 0.00 AC: 0 AN: 29924

South Asian (SAS) AF: 0.00 AC: 0 AN: 51785

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 40203

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3909

European-Non Finnish (NFE) AF: 0.0000603 AC: 50 AN: 829010

Other (OTH) AF: 0.00 AC: 0 AN: 45254

GnomAD4 genome AF: 0.0000179 AC: 2 AN: 111995 Hom.: 0 Cov.: 22 AF XY: 0.00 AC XY: 0 AN XY: 34169

African (AFR) AF: 0.00 AC: 0 AN: 30781

American (AMR) AF: 0.00 AC: 0 AN: 10605

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 2650

East Asian (EAS) AF: 0.00 AC: 0 AN: 3565

South Asian (SAS) AF: 0.00 AC: 0 AN: 2652

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 6104

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 240

European-Non Finnish (NFE) AF: 0.0000376 AC: 2 AN: 53200

Other (OTH) AF: 0.00 AC: 0 AN: 1511

Alfa AF: 0.000142 Hom.: 1

Bravo AF: 0.0000264

ESP6500AA AF: 0.00 AC: 0

ESP6500EA AF: 0.000149 AC: 1

ExAC AF: 0.0000247 AC: 3

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.068
BayesDel_addAF	Benign	-0.38	T
BayesDel_noAF	Benign	-0.68
CADD	Benign	11
DANN	Benign	0.74
DEOGEN2	Benign	0.13	T
FATHMM_MKL	Benign	0.34	N
LIST_S2	Benign	0.70	T
M_CAP	Uncertain	0.22	D
MetaRNN	Benign	0.14	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	-0.90	N
PhyloP100		1.5
PrimateAI	Benign	0.27	T
PROVEAN	Benign	0.010	N
REVEL	Benign	0.096
Sift	Benign	0.70	T
Sift4G	Benign	0.74	T
Polyphen		0.0010	B
Vest4		0.081
MVP		0.50
MPC		0.13
ClinPred		0.093	T
GERP RS		-0.89
Varity_R		0.039
gMVP		0.26
Mutation Taster		=91/9	polymorphism

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: rs370162233; hg19: chrX-111874820;