chr17-44804300-T-TA

Variant names:

• chr17-44804300-T-TA
• rs199789186
• NM_005497.4:c.*326dupT

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP6_Moderate BA1

The NM_005497.4(GJC1):​c.*326dupT variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.142 in 187,674 control chromosomes in the GnomAD database, including 1,519 homozygotes. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.14 (1494 hom., cov: 29)
  • Exomes 𝑓: 0.14 (25 hom.)
• Consequence: GJC1 NM_005497.4 3_prime_UTR
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.963
• Publications: 0 publications found

Genes affected

GJC1 (HGNC:4280): (gap junction protein gamma 1) This gene is a member of the connexin gene family. The encoded protein is a component of gap junctions, which are composed of arrays of intercellular channels that provide a route for the diffusion of low molecular weight materials from cell to cell. Alternatively spliced transcript variants encoding the same isoform have been described. [provided by RefSeq, Jul 2008]

ACMG classification

Our verdict: Benign. The variant received -10 ACMG points.

• BP6: Variant 17-44804300-T-TA is Benign according to our data. Variant chr17-44804300-T-TA is described in ClinVar as Benign. ClinVar VariationId is 1239515.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.191 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_005497.4. 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
	GJC1	NM_005497.4	MANE Select	c.*326dupT		3_prime_UTR	Exon 3 of 3	NP_005488.2	P36383
	GJC1	NM_001080383.2		c.*326dupT		3_prime_UTR	Exon 3 of 3	NP_001073852.1	P36383

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GJC1	ENST00000592524.6	TSL:2 MANE Select	c.*326dupT		3_prime_UTR	Exon 3 of 3	ENSP00000467201.1	P36383
	GJC1	ENST00000330514.4	TSL:2	c.*326dupT		3_prime_UTR	Exon 2 of 2	ENSP00000333193.3	P36383
	GJC1	ENST00000590758.3	TSL:3	c.*326dupT		3_prime_UTR	Exon 2 of 2	ENSP00000466339.1	P36383

Frequencies

GnomAD3 genomes AF: 0.144 AC: 20762 AN: 144256 Hom.: 1489 Cov.: 29

Gnomad AFR AF: 0.195

Gnomad AMI AF: 0.115

Gnomad AMR AF: 0.0991

Gnomad ASJ AF: 0.181

Gnomad EAS AF: 0.148

Gnomad SAS AF: 0.142

Gnomad FIN AF: 0.0994

Gnomad MID AF: 0.0714

Gnomad NFE AF: 0.128

Gnomad OTH AF: 0.126

GnomAD4 exome AF: 0.137 AC: 5947 AN: 43356 Hom.: 25 Cov.: 0 AF XY: 0.137 AC XY: 3008 AN XY: 21900

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.182 AC: 254 AN: 1398

American (AMR) AF: 0.119 AC: 279 AN: 2348

Ashkenazi Jewish (ASJ) AF: 0.176 AC: 277 AN: 1570

East Asian (EAS) AF: 0.144 AC: 363 AN: 2520

South Asian (SAS) AF: 0.128 AC: 135 AN: 1056

European-Finnish (FIN) AF: 0.114 AC: 261 AN: 2288

Middle Eastern (MID) AF: 0.117 AC: 22 AN: 188

European-Non Finnish (NFE) AF: 0.136 AC: 3947 AN: 29058

Other (OTH) AF: 0.140 AC: 409 AN: 2930

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome AF: 0.144 AC: 20778 AN: 144318 Hom.: 1494 Cov.: 29 AF XY: 0.141 AC XY: 9895 AN XY: 69980

African (AFR) AF: 0.195 AC: 7740 AN: 39684

American (AMR) AF: 0.0996 AC: 1434 AN: 14402

Ashkenazi Jewish (ASJ) AF: 0.181 AC: 613 AN: 3386

East Asian (EAS) AF: 0.148 AC: 742 AN: 5006

South Asian (SAS) AF: 0.142 AC: 643 AN: 4530

European-Finnish (FIN) AF: 0.0994 AC: 882 AN: 8876

Middle Eastern (MID) AF: 0.0704 AC: 19 AN: 270

European-Non Finnish (NFE) AF: 0.128 AC: 8357 AN: 65310

Other (OTH) AF: 0.125 AC: 247 AN: 1972

Alfa AF: 0.0278 Hom.: 14

ClinVar

ClinVar submissions

Significance: 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
PhyloP100		0.96
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: rs199789186; hg19: chr17-42881668;