7-128028018-C-T

Variant names:

• chr7-128028018-C-T
• rs3808058
• NM_022143.5:c.*661G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_022143.5(LRRC4):​c.*661G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.11 in 152,726 control chromosomes in the GnomAD database, including 1,187 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.11 (1186 hom., cov: 32)
  • Exomes 𝑓: 0.10 (1 hom.)
• Consequence: LRRC4 NM_022143.5 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.00400
• Publications: 8 publications found

Genes affected

LRRC4 (HGNC:15586): (leucine rich repeat containing 4) Predicted to be involved in modulation of chemical synaptic transmission and synapse organization. Predicted to act upstream of or within synapse organization. Predicted to be located in neuron spine and postsynaptic membrane. Predicted to be active in Schaffer collateral - CA1 synapse; glutamatergic synapse; and plasma membrane. Predicted to be integral component of postsynaptic density membrane. [provided by Alliance of Genome Resources, Apr 2022]

SND1 (HGNC:30646): (staphylococcal nuclease and tudor domain containing 1) This gene encodes a transcriptional co-activator that interacts with the acidic domain of Epstein-Barr virus nuclear antigen 2 (EBNA 2), a transcriptional activator that is required for B-lymphocyte transformation. Other transcription factors that interact with this protein are signal transducers and activators of transcription, STATs. This protein is also thought to be essential for normal cell growth. A similar protein in mammals and other organisms is a component of the RNA-induced silencing complex (RISC). [provided by RefSeq, Jul 2016]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.208 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_022143.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LRRC4	NM_022143.5	MANE Select	c.*661G>A		3_prime_UTR	Exon 2 of 2	NP_071426.1
	SND1	NM_014390.4	MANE Select	c.1779+36962C>T		intron	N/A	NP_055205.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LRRC4	ENST00000249363.4	TSL:1 MANE Select	c.*661G>A		3_prime_UTR	Exon 2 of 2	ENSP00000249363.3
	SND1	ENST00000354725.8	TSL:1 MANE Select	c.1779+36962C>T		intron	N/A	ENSP00000346762.3
	SND1	ENST00000486037.1	TSL:3	c.426+36962C>T		intron	N/A	ENSP00000419327.1

Frequencies

GnomAD3 genomes AF: 0.110 AC: 16660 AN: 152142 Hom.: 1181 Cov.: 32

Gnomad AFR AF: 0.0469

Gnomad AMI AF: 0.0965

Gnomad AMR AF: 0.213

Gnomad ASJ AF: 0.155

Gnomad EAS AF: 0.0779

Gnomad SAS AF: 0.176

Gnomad FIN AF: 0.110

Gnomad MID AF: 0.0886

Gnomad NFE AF: 0.120

Gnomad OTH AF: 0.111

GnomAD4 exome AF: 0.103 AC: 48 AN: 466 Hom.: 1 Cov.: 0 AF XY: 0.109 AC XY: 30 AN XY: 276

African (AFR) AC: 0 AN: 0

American (AMR) AF: 0.500 AC: 1 AN: 2

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AF: 0.00 AC: 0 AN: 2

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AF: 0.100 AC: 42 AN: 418

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.132 AC: 5 AN: 38

Other (OTH) AF: 0.00 AC: 0 AN: 6

GnomAD4 genome AF: 0.110 AC: 16684 AN: 152260 Hom.: 1186 Cov.: 32 AF XY: 0.113 AC XY: 8407 AN XY: 74450

African (AFR) AF: 0.0468 AC: 1945 AN: 41540

American (AMR) AF: 0.214 AC: 3270 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.155 AC: 538 AN: 3472

East Asian (EAS) AF: 0.0776 AC: 403 AN: 5190

South Asian (SAS) AF: 0.177 AC: 855 AN: 4826

European-Finnish (FIN) AF: 0.110 AC: 1164 AN: 10608

Middle Eastern (MID) AF: 0.0952 AC: 28 AN: 294

European-Non Finnish (NFE) AF: 0.120 AC: 8154 AN: 68010

Other (OTH) AF: 0.113 AC: 239 AN: 2112

Alfa AF: 0.114 Hom.: 1658

Bravo AF: 0.114

Asia WGS AF: 0.149 AC: 516 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	8.1
DANN	Benign	0.67
PhyloP100		-0.0040
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs3808058; hg19: chr7-127668071;