rs4714199

Variant names:

• chr6-38923292-T-G
• rs4714199
• NM_001206927.2:c.10790+107T>G

Your query was ambiguous. Multiple possible variants found:

• chr6-38923292-T-G
• chr6-38923292-T-A

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_001206927.2(DNAH8):​c.10790+107T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.136 in 1,362,986 control chromosomes in the GnomAD database, including 17,879 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.22 (5638 hom., cov: 32)
  • Exomes 𝑓: 0.13 (12241 hom.)
• Consequence: DNAH8 NM_001206927.2 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.224
• Publications: 5 publications found

Genes affected

DNAH8 (HGNC:2952): (dynein axonemal heavy chain 8) The protein encoded by this gene is a heavy chain of an axonemal dynein involved in sperm and respiratory cilia motility. Axonemal dyneins generate force through hydrolysis of ATP and binding to microtubules. [provided by RefSeq, Jan 2012]

DNAH8-AS1 (HGNC:40188): (DNAH8 antisense RNA 1)

ACMG classification

Our verdict: Benign. The variant received -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BP6: Variant 6-38923292-T-G is Benign according to our data. Variant chr6-38923292-T-G is described in ClinVar as Benign. ClinVar VariationId is 1224224.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.465 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001206927.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DNAH8	NM_001206927.2	MANE Select	c.10790+107T>G		intron	N/A	NP_001193856.1	A0A075B6F3
	DNAH8	NM_001371.4		c.10139+107T>G		intron	N/A	NP_001362.2	Q96JB1-1
	DNAH8-AS1	NR_038401.1		n.575A>C		non_coding_transcript_exon	Exon 4 of 5

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DNAH8	ENST00000327475.11	TSL:5 MANE Select	c.10790+107T>G		intron	N/A	ENSP00000333363.7	A0A075B6F3
	DNAH8	ENST00000359357.7	TSL:2	c.10139+107T>G		intron	N/A	ENSP00000352312.3	Q96JB1-1
	DNAH8	ENST00000449981.6	TSL:5	c.10790+107T>G		intron	N/A	ENSP00000415331.2	H0Y7V4

Frequencies

GnomAD3 genomes AF: 0.217 AC: 32930 AN: 152032 Hom.: 5624 Cov.: 32

Gnomad AFR AF: 0.471

Gnomad AMI AF: 0.116

Gnomad AMR AF: 0.141

Gnomad ASJ AF: 0.123

Gnomad EAS AF: 0.283

Gnomad SAS AF: 0.0745

Gnomad FIN AF: 0.104

Gnomad MID AF: 0.130

Gnomad NFE AF: 0.109

Gnomad OTH AF: 0.184

GnomAD4 exome AF: 0.125 AC: 151805 AN: 1210836 Hom.: 12241 Cov.: 15 AF XY: 0.123 AC XY: 73725 AN XY: 601714

African (AFR) AF: 0.478 AC: 12816 AN: 26818

American (AMR) AF: 0.130 AC: 3618 AN: 27816

Ashkenazi Jewish (ASJ) AF: 0.114 AC: 2244 AN: 19606

East Asian (EAS) AF: 0.275 AC: 10075 AN: 36702

South Asian (SAS) AF: 0.0667 AC: 4389 AN: 65756

European-Finnish (FIN) AF: 0.104 AC: 4275 AN: 41168

Middle Eastern (MID) AF: 0.0900 AC: 374 AN: 4154

European-Non Finnish (NFE) AF: 0.114 AC: 107068 AN: 937844

Other (OTH) AF: 0.136 AC: 6946 AN: 50972

GnomAD4 genome AF: 0.217 AC: 32976 AN: 152150 Hom.: 5638 Cov.: 32 AF XY: 0.211 AC XY: 15694 AN XY: 74376

African (AFR) AF: 0.471 AC: 19528 AN: 41474

American (AMR) AF: 0.141 AC: 2155 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.123 AC: 427 AN: 3470

East Asian (EAS) AF: 0.282 AC: 1460 AN: 5172

South Asian (SAS) AF: 0.0735 AC: 354 AN: 4818

European-Finnish (FIN) AF: 0.104 AC: 1105 AN: 10598

Middle Eastern (MID) AF: 0.136 AC: 40 AN: 294

European-Non Finnish (NFE) AF: 0.109 AC: 7416 AN: 68014

Other (OTH) AF: 0.182 AC: 385 AN: 2114

Alfa AF: 0.142 Hom.: 9918

Bravo AF: 0.235

Asia WGS AF: 0.183 AC: 636 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	2.4
DANN	Benign	0.79
PhyloP100		0.22
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: rs4714199; hg19: chr6-38891068; COSMIC: COSV59422084; COSMIC: COSV59422084;