rs6085297

Positions:

• chr20-5862833-C-T

Variant summary

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

The NM_152504.4(SHLD1):​c.179-191C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.138 in 152,184 control chromosomes in the GnomAD database, including 1,605 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 0.14 (1605 hom., cov: 33)
• Consequence: SHLD1 NM_152504.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.294

Genes affected

SHLD1 (HGNC:26318): (shieldin complex subunit 1) Involved in negative regulation of double-strand break repair via homologous recombination; positive regulation of double-strand break repair via nonhomologous end joining; and positive regulation of isotype switching. Located in site of double-strand break. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.171 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SHLD1	NM_152504.4	c.179-191C>T		intron_variant		ENST00000303142.11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SHLD1	ENST00000303142.11	c.179-191C>T		intron_variant		1	NM_152504.4	P1
SHLD1	ENST00000442185.1	c.320-191C>T		intron_variant		3
SHLD1	ENST00000445603.1	c.179-191C>T		intron_variant		3

Frequencies

GnomAD3 genomes AF: 0.138 AC: 21052 AN: 152066 Hom.: 1606 Cov.: 33

Gnomad AFR AF: 0.111

Gnomad AMI AF: 0.129

Gnomad AMR AF: 0.148

Gnomad ASJ AF: 0.121

Gnomad EAS AF: 0.000770

Gnomad SAS AF: 0.0948

Gnomad FIN AF: 0.101

Gnomad MID AF: 0.136

Gnomad NFE AF: 0.173

Gnomad OTH AF: 0.151

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.138 AC: 21061 AN: 152184 Hom.: 1605 Cov.: 33 AF XY: 0.133 AC XY: 9885 AN XY: 74416

Gnomad4 AFR AF: 0.110

Gnomad4 AMR AF: 0.148

Gnomad4 ASJ AF: 0.121

Gnomad4 EAS AF: 0.000772

Gnomad4 SAS AF: 0.0959

Gnomad4 FIN AF: 0.101

Gnomad4 NFE AF: 0.173

Gnomad4 OTH AF: 0.149

Alfa AF: 0.163 Hom.: 2905

Bravo AF: 0.141

Asia WGS AF: 0.0490 AC: 170 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	2.1
DANN	Benign	0.63

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: rs6085297; hg19: chr20-5843479;