chr2-7421755-C-T

Variant names:

• chr2-7421755-C-T
• rs1367272
• ENST00000419713.5:n.117+368C>T

Variant summary

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

The ENST00000450695.2(ENSG00000229727):​n.179C>T variant causes a non coding transcript exon change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.812 in 152,138 control chromosomes in the GnomAD database, including 50,568 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 0.81 (50563 hom., cov: 31)
  • Exomes 𝑓: 0.92 (5 hom.)
• Consequence: ENSG00000229727 ENST00000450695.2 non_coding_transcript_exon
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.120
• Publications: 2 publications found

Genes affected

ENSG00000229727 (HGNC:):

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.828 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000450695.2. 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
	LOC100506274	NR_038432.1		n.127+368C>T		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ENSG00000229727	ENST00000419713.5	TSL:1	n.117+368C>T		intron	N/A
	ENSG00000229727	ENST00000450695.2	TSL:4	n.179C>T		non_coding_transcript_exon	Exon 2 of 8
	ENSG00000229727	ENST00000657879.1		n.179C>T		non_coding_transcript_exon	Exon 2 of 9

Frequencies

GnomAD3 genomes AF: 0.812 AC: 123459 AN: 152008 Hom.: 50523 Cov.: 31

Gnomad AFR AF: 0.835

Gnomad AMI AF: 0.885

Gnomad AMR AF: 0.781

Gnomad ASJ AF: 0.885

Gnomad EAS AF: 0.524

Gnomad SAS AF: 0.732

Gnomad FIN AF: 0.779

Gnomad MID AF: 0.813

Gnomad NFE AF: 0.833

Gnomad OTH AF: 0.828

GnomAD4 exome AF: 0.917 AC: 11 AN: 12 Hom.: 5 Cov.: 0 AF XY: 0.900 AC XY: 9 AN XY: 10

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

African (AFR) AF: 1.00 AC: 2 AN: 2

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AF: 1.00 AC: 2 AN: 2

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AC: 0 AN: 0

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 1.00 AC: 6 AN: 6

Other (OTH) AF: 0.500 AC: 1 AN: 2

⚠️ 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: 0.812 AC: 123555 AN: 152126 Hom.: 50563 Cov.: 31 AF XY: 0.810 AC XY: 60199 AN XY: 74362

African (AFR) AF: 0.835 AC: 34655 AN: 41506

American (AMR) AF: 0.781 AC: 11919 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.885 AC: 3070 AN: 3468

East Asian (EAS) AF: 0.524 AC: 2694 AN: 5146

South Asian (SAS) AF: 0.733 AC: 3538 AN: 4828

European-Finnish (FIN) AF: 0.779 AC: 8246 AN: 10588

Middle Eastern (MID) AF: 0.803 AC: 236 AN: 294

European-Non Finnish (NFE) AF: 0.833 AC: 56644 AN: 68000

Other (OTH) AF: 0.826 AC: 1746 AN: 2114

Alfa AF: 0.826 Hom.: 114589

Bravo AF: 0.812

Asia WGS AF: 0.635 AC: 2209 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	2.0
DANN	Benign	0.39
PhyloP100		0.12

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs1367272;

hg19: chr2-7561886;