14-105909907-G-A

Position:

• chr14-105909907-G-A

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_Strong BP6_Moderate BS2

The ENST00000430425.1(IGHD1-7):​c.17C>T​(p.Ter6=) variant causes a incomplete terminal codon, coding sequence change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000234 in 734,444 control chromosomes in the GnomAD database, including 17 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.00043 (7 hom., cov: 29)
  • Exomes 𝑓: 0.00019 (10 hom.)
• Consequence: IGHD1-7 ENST00000430425.1 incomplete_terminal_codon, coding_sequence
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -2.03

Genes affected

IGHD1-7 (HGNC:5486): (immunoglobulin heavy diversity 1-7)

FAM30A (HGNC:19955): (family with sequence similarity 30 member A)

ACMG classification

Verdict is Benign. Variant got -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BP6: Variant 14-105909907-G-A is Benign according to our data. Variant chr14-105909907-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 2644928.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High Homozygotes in GnomAd4 at 7 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
IGHD1-7	ENST00000430425.1	c.17C>T	p.Ter6=	incomplete_terminal_codon_variant, coding_sequence_variant	1/1			P1
FAM30A	ENST00000693413.1	n.116-11156G>A		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes AF: 0.000408 AC: 56 AN: 137326 Hom.: 6 Cov.: 29

Gnomad AFR AF: 0.000249

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000154

Gnomad ASJ AF: 0.00557

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00125

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.0108

Gnomad NFE AF: 0.000273

Gnomad OTH AF: 0.00107

GnomAD4 exome AF: 0.000189 AC: 113 AN: 597084 Hom.: 10 Cov.: 0 AF XY: 0.000218 AC XY: 71 AN XY: 325514

Gnomad4 AFR exome AF: 0.000239

Gnomad4 AMR exome AF: 0.0000947

Gnomad4 ASJ exome AF: 0.00107

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.000403

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000616

Gnomad4 OTH exome AF: 0.000223

GnomAD4 genome AF: 0.000430 AC: 59 AN: 137360 Hom.: 7 Cov.: 29 AF XY: 0.000422 AC XY: 28 AN XY: 66326

Gnomad4 AFR AF: 0.000332

Gnomad4 AMR AF: 0.000154

Gnomad4 ASJ AF: 0.00557

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00125

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000273

Gnomad4 OTH AF: 0.00106

Alfa AF: 0.000422 Hom.: 0

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Dec 01, 2022

ENSG00000288730: BS2 -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	13
DANN	Benign	0.76

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: rs1368381473; hg19: chr14-106375766;