rs6944446

chr7-128027463-G-A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_022143.5(LRRC4):c.*1216C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.571 in 152,274 control chromosomes in the GnomAD database, including 25,799 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 0.57 (25745 hom., cov: 31)
  • Exomes 𝑓: 0.47 (54 hom.)
• Consequence: LRRC4 NM_022143.5 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0250

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

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.711 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
LRRC4	NM_022143.5	c.*1216C>T		3_prime_UTR_variant	2/2	ENST00000249363.4
SND1	NM_014390.4	c.1779+36407G>A		intron_variant		ENST00000354725.8
LRRC4	XM_011516461.4	c.*1216C>T		3_prime_UTR_variant	3/3
LRRC4	XM_047420695.1	c.*1216C>T		3_prime_UTR_variant	3/3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
LRRC4	ENST00000249363.4	c.*1216C>T		3_prime_UTR_variant	2/2	1	NM_022143.5	P1
SND1	ENST00000354725.8	c.1779+36407G>A		intron_variant		1	NM_014390.4	P1

Frequencies

GnomAD3 genomes AF: 0.571 AC: 86673 AN: 151722 Hom.: 25721 Cov.: 31

Gnomad AFR AF: 0.718

Gnomad AMI AF: 0.510

Gnomad AMR AF: 0.566

Gnomad ASJ AF: 0.521

Gnomad EAS AF: 0.216

Gnomad SAS AF: 0.544

Gnomad FIN AF: 0.470

Gnomad MID AF: 0.535

Gnomad NFE AF: 0.532

Gnomad OTH AF: 0.561

GnomAD4 exome AF: 0.472 AC: 206 AN: 436 Hom.: 54 Cov.: 0 AF XY: 0.485 AC XY: 129 AN XY: 266

Gnomad4 AFR exome AF: 1.00

Gnomad4 FIN exome AF: 0.466

Gnomad4 NFE exome AF: 0.583

Gnomad4 OTH exome AF: 0.500

GnomAD4 genome AF: 0.571 AC: 86754 AN: 151838 Hom.: 25745 Cov.: 31 AF XY: 0.565 AC XY: 41894 AN XY: 74182

Gnomad4 AFR AF: 0.718

Gnomad4 AMR AF: 0.567

Gnomad4 ASJ AF: 0.521

Gnomad4 EAS AF: 0.215

Gnomad4 SAS AF: 0.543

Gnomad4 FIN AF: 0.470

Gnomad4 NFE AF: 0.531

Gnomad4 OTH AF: 0.561

Alfa AF: 0.540 Hom.: 22494

Bravo AF: 0.581

Asia WGS AF: 0.413 AC: 1438 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
Cadd	Benign	5.9
Dann	Benign	0.76

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: rs6944446; hg19: chr7-127667516; COSMIC: COSV50815731; COSMIC: COSV50815731;