rs1343178

Positions:

• chr20-5862794-C-G
• chr20-5862794-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.179-230C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.727 in 152,158 control chromosomes in the GnomAD database, including 40,344 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 0.73 (40344 hom., cov: 32)
• Consequence: SHLD1 NM_152504.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0550

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=-0.9).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.785 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SHLD1	NM_152504.4	c.179-230C>G		intron_variant		ENST00000303142.11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SHLD1	ENST00000303142.11	c.179-230C>G		intron_variant		1	NM_152504.4	P1
SHLD1	ENST00000442185.1	c.320-230C>G		intron_variant		3
SHLD1	ENST00000445603.1	c.179-230C>G		intron_variant		3

Frequencies

GnomAD3 genomes AF: 0.727 AC: 110489 AN: 152040 Hom.: 40316 Cov.: 32

Gnomad AFR AF: 0.792

Gnomad AMI AF: 0.665

Gnomad AMR AF: 0.744

Gnomad ASJ AF: 0.718

Gnomad EAS AF: 0.761

Gnomad SAS AF: 0.663

Gnomad FIN AF: 0.655

Gnomad MID AF: 0.718

Gnomad NFE AF: 0.698

Gnomad OTH AF: 0.721

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

GnomAD4 genome AF: 0.727 AC: 110572 AN: 152158 Hom.: 40344 Cov.: 32 AF XY: 0.724 AC XY: 53862 AN XY: 74370

Gnomad4 AFR AF: 0.792

Gnomad4 AMR AF: 0.744

Gnomad4 ASJ AF: 0.718

Gnomad4 EAS AF: 0.761

Gnomad4 SAS AF: 0.662

Gnomad4 FIN AF: 0.655

Gnomad4 NFE AF: 0.698

Gnomad4 OTH AF: 0.722

Alfa AF: 0.570 Hom.: 1209

Bravo AF: 0.739

Asia WGS AF: 0.725 AC: 2520 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	1.2
DANN	Benign	0.39

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: rs1343178; hg19: chr20-5843440;