NM_001378107.1:c.1725+718C>T

Variant names:

• chr2-135650721-C-T
• rs4954278
• NM_001378107.1:c.1725+718C>T

Variant summary

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

The NM_001378107.1(R3HDM1):​c.1725+718C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0915 in 980,812 control chromosomes in the GnomAD database, including 6,433 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 0.16 (2730 hom., cov: 32)
  • Exomes 𝑓: 0.078 (3703 hom.)
• Consequence: R3HDM1 NM_001378107.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.769

Genes affected

R3HDM1 (HGNC:9757): (R3H domain containing 1) Enables RNA binding activity. [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=-0.47).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.306 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
R3HDM1	NM_001378107.1	c.1725+718C>T		intron_variant	Intron 17 of 26	ENST00000683871.1	NP_001365036.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
R3HDM1	ENST00000683871.1	c.1725+718C>T		intron_variant	Intron 17 of 26		NM_001378107.1	ENSP00000506980.1

Frequencies

GnomAD3 genomes AF: 0.165 AC: 25061 AN: 151896 Hom.: 2731 Cov.: 32

Gnomad AFR AF: 0.282

Gnomad AMI AF: 0.0747

Gnomad AMR AF: 0.212

Gnomad ASJ AF: 0.109

Gnomad EAS AF: 0.167

Gnomad SAS AF: 0.321

Gnomad FIN AF: 0.110

Gnomad MID AF: 0.280

Gnomad NFE AF: 0.0840

Gnomad OTH AF: 0.166

GnomAD4 exome AF: 0.0780 AC: 64644 AN: 828798 Hom.: 3703 Cov.: 30 AF XY: 0.0781 AC XY: 29898 AN XY: 382892

Gnomad4 AFR exome AF: 0.299

Gnomad4 AMR exome AF: 0.204

Gnomad4 ASJ exome AF: 0.119

Gnomad4 EAS exome AF: 0.171

Gnomad4 SAS exome AF: 0.301

Gnomad4 FIN exome AF: 0.101

Gnomad4 NFE exome AF: 0.0664

Gnomad4 OTH exome AF: 0.105

GnomAD4 genome AF: 0.165 AC: 25076 AN: 152014 Hom.: 2730 Cov.: 32 AF XY: 0.169 AC XY: 12581 AN XY: 74300

Gnomad4 AFR AF: 0.282

Gnomad4 AMR AF: 0.211

Gnomad4 ASJ AF: 0.109

Gnomad4 EAS AF: 0.167

Gnomad4 SAS AF: 0.320

Gnomad4 FIN AF: 0.110

Gnomad4 NFE AF: 0.0840

Gnomad4 OTH AF: 0.166

Alfa AF: 0.105 Hom.: 1582

Bravo AF: 0.173

Asia WGS AF: 0.253 AC: 880 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.47
CADD	Benign	8.6
DANN	Benign	0.81

Splicing

Name	Calibrated prediction	Score	Prediction
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: rs4954278; hg19: chr2-136408291;