20-5861872-T-C

Variant names:

• chr20-5861872-T-C
• rs6053754
• NM_152504.4:c.179-1152T>C

Variant summary

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

The NM_152504.4(SHLD1):​c.179-1152T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.304 in 152,040 control chromosomes in the GnomAD database, including 7,250 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 0.30 (7250 hom., cov: 32)
• Consequence: SHLD1 NM_152504.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.255

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=-0.91).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.441 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SHLD1	NM_152504.4	c.179-1152T>C		intron_variant	Intron 2 of 2	ENST00000303142.11	NP_689717.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SHLD1	ENST00000303142.11	c.179-1152T>C		intron_variant	Intron 2 of 2	1	NM_152504.4	ENSP00000305875.6
SHLD1	ENST00000442185.1	c.320-1152T>C		intron_variant	Intron 3 of 3	3		ENSP00000410534.1
SHLD1	ENST00000445603.1	c.179-1152T>C		intron_variant	Intron 3 of 3	3		ENSP00000399331.1

Frequencies

GnomAD3 genomes AF: 0.304 AC: 46144 AN: 151922 Hom.: 7233 Cov.: 32

Gnomad AFR AF: 0.302

Gnomad AMI AF: 0.202

Gnomad AMR AF: 0.377

Gnomad ASJ AF: 0.253

Gnomad EAS AF: 0.456

Gnomad SAS AF: 0.361

Gnomad FIN AF: 0.219

Gnomad MID AF: 0.288

Gnomad NFE AF: 0.289

Gnomad OTH AF: 0.318

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

GnomAD4 genome AF: 0.304 AC: 46194 AN: 152040 Hom.: 7250 Cov.: 32 AF XY: 0.304 AC XY: 22589 AN XY: 74334

Gnomad4 AFR AF: 0.302

Gnomad4 AMR AF: 0.377

Gnomad4 ASJ AF: 0.253

Gnomad4 EAS AF: 0.456

Gnomad4 SAS AF: 0.361

Gnomad4 FIN AF: 0.219

Gnomad4 NFE AF: 0.289

Gnomad4 OTH AF: 0.325

Alfa AF: 0.293 Hom.: 8846

Bravo AF: 0.316

Asia WGS AF: 0.433 AC: 1505 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	3.9
DANN	Benign	0.33

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: rs6053754; hg19: chr20-5842518;