ENST00000360168.7:c.-204A>G

Variant names:

• chr12-6375164-T-C
• rs72645129
• ENST00000360168.7:c.-204A>G

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BS1 BS2

The ENST00000360168.7(SCNN1A):​c.-204A>G variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00246 in 1,459,988 control chromosomes in the GnomAD database, including 82 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.013 (43 hom., cov: 32)
  • Exomes 𝑓: 0.0013 (39 hom.)
• Consequence: SCNN1A ENST00000360168.7 5_prime_UTR
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.171
• Publications: 0 publications found

Genes affected

SCNN1A (HGNC:10599): (sodium channel epithelial 1 subunit alpha) Nonvoltage-gated, amiloride-sensitive, sodium channels control fluid and electrolyte transport across epithelia in many organs. These channels are heteromeric complexes consisting of 3 subunits: alpha, beta, and gamma. This gene encodes the alpha subunit, and mutations in this gene have been associated with pseudohypoaldosteronism type 1 (PHA1), a rare salt wasting disease resulting from target organ unresponsiveness to mineralocorticoids. Alternatively spliced transcript variants encoding different isoforms have been described for this gene. [provided by RefSeq, Apr 2009]

LTBR (HGNC:6718): (lymphotoxin beta receptor) This gene encodes a member of the tumor necrosis factor receptor superfamily. The major ligands of this receptor include lymphotoxin alpha/beta and tumor necrosis factor ligand superfamily member 14. The encoded protein plays a role in signalling during the development of lymphoid and other organs, lipid metabolism, immune response, and programmed cell death. Activity of this receptor has also been linked to carcinogenesis. Alternatively spliced transcript variants encoding multiple isoforms have been observed. [provided by RefSeq, Aug 2012]

ACMG classification

Our verdict: Benign. The variant received -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.8).
• BP6: Variant 12-6375164-T-C is Benign according to our data. Variant chr12-6375164-T-C is described in ClinVar as Likely_benign. ClinVar VariationId is 1191688.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.0126 (1913/152224) while in subpopulation AFR AF = 0.0434 (1801/41528). AF 95% confidence interval is 0.0417. There are 43 homozygotes in GnomAd4. There are 881 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 43 AR,Unknown,AD gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000360168.7. 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
	SCNN1A	NM_001038.6	MANE Select	c.-54-327A>G		intron	N/A	NP_001029.1	P37088-1
	SCNN1A	NM_001159576.2		c.-204A>G		5_prime_UTR	Exon 1 of 12	NP_001153048.1	P37088-2
	LTBR	NM_001270987.2		c.-392T>C		5_prime_UTR	Exon 1 of 10	NP_001257916.1	P36941-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SCNN1A	ENST00000360168.7	TSL:1	c.-204A>G		5_prime_UTR	Exon 1 of 12	ENSP00000353292.3	P37088-2
	SCNN1A	ENST00000228916.7	TSL:1 MANE Select	c.-54-327A>G		intron	N/A	ENSP00000228916.2	P37088-1
	SCNN1A	ENST00000868231.1		c.-211A>G		5_prime_UTR	Exon 1 of 13	ENSP00000538290.1

Frequencies

GnomAD3 genomes AF: 0.0126 AC: 1911 AN: 152106 Hom.: 42 Cov.: 32

Gnomad AFR AF: 0.0434

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00452

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.000206

Gnomad OTH AF: 0.0134

GnomAD4 exome AF: 0.00128 AC: 1674 AN: 1307764 Hom.: 39 Cov.: 31 AF XY: 0.00115 AC XY: 732 AN XY: 637016

African (AFR) AF: 0.0443 AC: 1294 AN: 29212

American (AMR) AF: 0.00303 AC: 79 AN: 26098

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 20110

East Asian (EAS) AF: 0.0000570 AC: 2 AN: 35088

South Asian (SAS) AF: 0.000122 AC: 8 AN: 65722

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 30282

Middle Eastern (MID) AF: 0.00380 AC: 14 AN: 3684

European-Non Finnish (NFE) AF: 0.000118 AC: 123 AN: 1043086

Other (OTH) AF: 0.00283 AC: 154 AN: 54482

GnomAD4 genome AF: 0.0126 AC: 1913 AN: 152224 Hom.: 43 Cov.: 32 AF XY: 0.0118 AC XY: 881 AN XY: 74438

African (AFR) AF: 0.0434 AC: 1801 AN: 41528

American (AMR) AF: 0.00451 AC: 69 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5174

South Asian (SAS) AF: 0.00 AC: 0 AN: 4820

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10612

Middle Eastern (MID) AF: 0.00340 AC: 1 AN: 294

European-Non Finnish (NFE) AF: 0.000206 AC: 14 AN: 68002

Other (OTH) AF: 0.0133 AC: 28 AN: 2112

Alfa AF: 0.00860 Hom.: 0

Bravo AF: 0.0137

Asia WGS AF: 0.00318 AC: 11 AN: 3478

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, single submitter

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

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	9.0
DANN	Benign	0.83
PhyloP100		-0.17
PromoterAI		0.084	Neutral
Mutation Taster		=300/0	polymorphism

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: rs72645129; hg19: chr12-6484330;