chr3-149035005-A-G

Variant names:

• chr3-149035005-A-G
• rs187819846
• NM_003071.4:c.2797-7T>C

Variant summary

Our verdict is Benign. The variant received -9 ACMG points: 0P and 9B. BP4_Strong BP6 BS2

The NM_003071.4(HLTF):​c.2797-7T>C variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000492 in 1,604,932 control chromosomes in the GnomAD database, including 3 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Likely benign (no stars).

• Frequency:
  • Genomes: 𝑓 0.00098 (2 hom., cov: 32)
  • Exomes 𝑓: 0.00044 (1 hom.)
• Consequence: HLTF NM_003071.4 splice_region, intron
• Scores: Splicing: ADA: 0.0001680
• Clinical Significance: Likely benign no assertion criteria provided B:1
• Conservation: PhyloP100: 1.25

Genes affected

HLTF (HGNC:11099): (helicase like transcription factor) This gene encodes a member of the SWI/SNF family. Members of this family have helicase and ATPase activities and are thought to regulate transcription of certain genes by altering the chromatin structure around those genes. The encoded protein contains a RING finger DNA binding motif. Two transcript variants encoding the same protein have been found for this gene. However, use of an alternative translation start site produces an isoform that is truncated at the N-terminus compared to the full-length protein. [provided by RefSeq, Jul 2008]

ACMG classification

Our verdict: Benign. The variant received -9 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.74).
• BP6: Variant 3-149035005-A-G is Benign according to our data. Variant chr3-149035005-A-G is described in ClinVar as [Likely_benign]. Clinvar id is 3052330.Status of the report is no_assertion_criteria_provided, 0 stars.
• BS2: High Homozygotes in GnomAd4 at 2 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
HLTF	NM_003071.4	c.2797-7T>C		splice_region_variant, intron_variant	Intron 23 of 24	ENST00000310053.10	NP_003062.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
HLTF	ENST00000310053.10	c.2797-7T>C		splice_region_variant, intron_variant	Intron 23 of 24	1	NM_003071.4	ENSP00000308944.5

Frequencies

GnomAD3 genomes AF: 0.000979 AC: 149 AN: 152224 Hom.: 2 Cov.: 32

Gnomad AFR AF: 0.00135

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00373

Gnomad ASJ AF: 0.00115

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.000353

Gnomad OTH AF: 0.00334

GnomAD2 exomes AF: 0.000660 AC: 166 AN: 251382 AF XY: 0.000581

Gnomad AFR exome AF: 0.00117

Gnomad AMR exome AF: 0.00197

Gnomad ASJ exome AF: 0.000893

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000501

Gnomad OTH exome AF: 0.00212

GnomAD4 exome AF: 0.000441 AC: 641 AN: 1452590 Hom.: 1 Cov.: 27 AF XY: 0.000415 AC XY: 300 AN XY: 723362

Gnomad4 AFR exome AF: 0.00111 AC: 37 AN: 33310

Gnomad4 AMR exome AF: 0.00221 AC: 99 AN: 44708

Gnomad4 ASJ exome AF: 0.00111 AC: 29 AN: 26078

Gnomad4 EAS exome AF: 0.00 AC: 0 AN: 39606

Gnomad4 SAS exome AF: 0.00 AC: 0 AN: 86076

Gnomad4 FIN exome AF: 0.00 AC: 0 AN: 53412

Gnomad4 NFE exome AF: 0.000378 AC: 417 AN: 1103596

Gnomad4 Remaining exome AF: 0.000816 AC: 49 AN: 60056

GnomAD4 genome AF: 0.000978 AC: 149 AN: 152342 Hom.: 2 Cov.: 32 AF XY: 0.00103 AC XY: 77 AN XY: 74508

Gnomad4 AFR AF: 0.00135 AC: 0.00134661 AN: 0.00134661

Gnomad4 AMR AF: 0.00373 AC: 0.00372549 AN: 0.00372549

Gnomad4 ASJ AF: 0.00115 AC: 0.00115207 AN: 0.00115207

Gnomad4 EAS AF: 0.00 AC: 0 AN: 0

Gnomad4 SAS AF: 0.00 AC: 0 AN: 0

Gnomad4 FIN AF: 0.00 AC: 0 AN: 0

Gnomad4 NFE AF: 0.000353 AC: 0.000352786 AN: 0.000352786

Gnomad4 OTH AF: 0.00331 AC: 0.00330813 AN: 0.00330813

Alfa AF: 0.000752 Hom.: 0

Bravo AF: 0.00127

EpiCase AF: 0.000874

EpiControl AF: 0.000652

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

Submissions by phenotype

HLTF-related disorder Benign:1

Feb 23, 2021

PreventionGenetics, part of Exact Sciences

Significance: Likely benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.74
CADD	Benign	12
DANN	Benign	0.58
Mutation Taster		=100/0	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.00017
dbscSNV1_RF	Benign	0.0
SpliceAI score (max)		0.030		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: rs187819846; hg19: chr3-148752792;