rs7271920

Variant names:

• chr20-5859724-C-T
• rs7271920
• NM_152504.4:c.179-3300C>T

Variant summary

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

The NM_152504.4(SHLD1):​c.179-3300C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0997 in 152,236 control chromosomes in the GnomAD database, including 793 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 0.10 (793 hom., cov: 32)
• Consequence: SHLD1 NM_152504.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.190
• Publications: 3 publications found

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

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.111 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SHLD1	NM_152504.4	c.179-3300C>T		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.179-3300C>T		intron_variant	Intron 2 of 2	1	NM_152504.4	ENSP00000305875.6
SHLD1	ENST00000442185.1	c.320-3300C>T		intron_variant	Intron 3 of 3	3		ENSP00000410534.1
SHLD1	ENST00000445603.1	c.179-3300C>T		intron_variant	Intron 3 of 3	3		ENSP00000399331.1

Frequencies

GnomAD3 genomes AF: 0.0998 AC: 15181 AN: 152118 Hom.: 794 Cov.: 32

Gnomad AFR AF: 0.0828

Gnomad AMI AF: 0.128

Gnomad AMR AF: 0.0792

Gnomad ASJ AF: 0.135

Gnomad EAS AF: 0.0603

Gnomad SAS AF: 0.0601

Gnomad FIN AF: 0.131

Gnomad MID AF: 0.0918

Gnomad NFE AF: 0.113

Gnomad OTH AF: 0.104

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

GnomAD4 genome AF: 0.0997 AC: 15182 AN: 152236 Hom.: 793 Cov.: 32 AF XY: 0.0990 AC XY: 7369 AN XY: 74428

African (AFR) AF: 0.0827 AC: 3436 AN: 41538

American (AMR) AF: 0.0791 AC: 1210 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.135 AC: 467 AN: 3466

East Asian (EAS) AF: 0.0604 AC: 313 AN: 5182

South Asian (SAS) AF: 0.0600 AC: 289 AN: 4820

European-Finnish (FIN) AF: 0.131 AC: 1388 AN: 10600

Middle Eastern (MID) AF: 0.0850 AC: 25 AN: 294

European-Non Finnish (NFE) AF: 0.113 AC: 7720 AN: 68018

Other (OTH) AF: 0.103 AC: 217 AN: 2114

Alfa AF: 0.105 Hom.: 159

Bravo AF: 0.0948

Asia WGS AF: 0.0600 AC: 209 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	1.1
DANN	Benign	0.40
PhyloP100		-0.19
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: rs7271920; hg19: chr20-5840370;